CA CANCER J CLIN 2018;68:250–281

Colorectal Cancer Screening for Average-Risk Adults:

2018 Guideline Update From the American Cancer Society
Andrew M.D. Wolf, MD1; Elizabeth T.H. Fontham, MPH, DrPH2; Timothy R. Church, PhD3; Christopher R. Flowers, MD, MS4;
Carmen E. Guerra, MD5; Samuel J. LaMonte, MD6; Ruth Etzioni, PhD7; Matthew T. McKenna, MD8; Kevin C. Oeffinger, MD9;
Ya-Chen Tina Shih, PhD10; Louise C. Walter, MD11; Kimberly S. Andrews, BA12; Otis W. Brawley, MD13;
Durado Brooks, MD, MPH14; Stacey A. Fedewa, PhD, MPH15; Deana Manassaram-Baptiste, PhD, MPH16;
Rebecca L. Siegel, MPH17; Richard C. Wender, MD18; Robert A. Smith, PhD19

1
Associate Professor and Attending Physician,
University of Virginia School of Medicine,
Charlottesville, VA; 2Emeritus Professor,
Louisiana State University School of Public
Health, New Orleans, LA; 3Professor, University
of Minnesota and Masonic Cancer Center,
Minneapolis, MN; 4Professor and Attending
Physician, Emory University School of Medicine
and Winship Cancer Institute, Atlanta, GA;
5
Associate Professor of Medicine of the
Perelman School of Medicine and Attending
Physician, University of Pennsylvania Medical
Center, Philadelphia, PA; 6Independent retired
physician and patient advocate; 7Biostatistician,
University of Washington and the Fred
Hutchinson Cancer Research Center, Seattle,
WA; 8Professor and Director, Division of
Preventive Medicine, Department of Family and
Preventive Medicine, Emory University School of
Medicine, Atlanta, GA; 9Professor and Director
of the Duke Center for Onco-Primary Care,
Durham, NC; 10Professor, Health Services
Research, The University of Texas MD Anderson
Cancer Center, Houston, TX; 11Professor and
Attending Physician, University of California, San
Francisco and San Francisco VA Medical
Center, San Francisco, CA; 12Director, Cancer
Control Department, American Cancer Society,
Atlanta, GA; 13Chief Medical and Scientific
Officer and Executive Vice President-Research,
American Cancer Society, Atlanta, GA; 14Vice
President, Cancer Control Interventions, Cancer
Control Department, American Cancer Society,
Atlanta, GA; 15Strategic Director for Risk Factor
Screening and Surveillance, American Cancer
Society, Atlanta, GA; 16Director, Cancer Control
Department, American Cancer Society, Atlanta,
GA; 17Strategic Director, Surveillance
Information Services, American Cancer Society,
Atlanta, GA; 18Chief Cancer Control Officer,
American Cancer Society, Atlanta, GA; 19Vice
President, Cancer Screening, Cancer Control
Department, American Cancer Society, Atlanta,
GA.
Additional supporting information may be found
online in the Supporting Information section at the
end of the article.
Abstract: In the United States, colorectal cancer (CRC) is the fourth most common
cancer diagnosed among adults and the second leading cause of death from cancer.
For this guideline update, the American Cancer Society (ACS) used an existing sys-
tematic evidence review of the CRC screening literature and microsimulation model-
ing analyses, including a new evaluation of the age to begin screening by race and
sex and additional modeling that incorporates changes in US CRC incidence. Screen-
ing with any one of multiple options is associated with a significant reduction in CRC
incidence through the detection and removal of adenomatous polyps and other pre-
cancerous lesions and with a reduction in mortality through incidence reduction and
early detection of CRC. Results from modeling analyses identified efficient and
model-recommendable strategies that started screening at age 45 years. The ACS
Guideline Development Group applied the Grades of Recommendations, Assess-
ment, Development, and Evaluation (GRADE) criteria in developing and rating the
recommendations. The ACS recommends that adults aged 45 years and older with
an average risk of CRC undergo regular screening with either a high-sensitivity stool-
based test or a structural (visual) examination, depending on patient preference and
test availability. As a part of the screening process, all positive results on noncolono-
scopy screening tests should be followed up with timely colonoscopy. The recom-
mendation to begin screening at age 45 years is a qualified recommendation. The
recommendation for regular screening in adults aged 50 years and older is a strong
recommendation. The ACS recommends (qualified recommendations) that: 1) average-
risk adults in good health with a life expectancy of more than 10 years continue
CRC screening through the age of 75 years; 2) clinicians individualize CRC screening
decisions for individuals aged 76 through 85 years based on patient preferences, life
expectancy, health status, and prior screening history; and 3) clinicians discourage
individuals older than 85 years from continuing CRC screening. The options for CRC
screening are: fecal immunochemical test annually; high-sensitivity, guaiac-based
fecal occult blood test annually; multitarget stool DNA test every 3 years;
colonoscopy every 10 years; computed tomography colonography every 5 years;
and flexible sigmoidoscopy every 5 years. CA Cancer J Clin 2018;68:250-281.
C 2018 American Cancer Society.
V
Keywords: adenoma, colonoscopy, computed tomography colonoscopy, colorectal
and rectal neoplasms, mass screening and early detection, mortality, occult blood,
radiography, sigmoidoscopy, stool testing

Corresponding author: Robert A. Smith, PhD, Vice President, Cancer Screening, Cancer Control Department, American Cancer Society, 250 Williams Street, Suite 600, Atlanta, GA
30303; robert.smith@cancer.org

Members of the American Cancer Society Guideline Development Group (GDG) serve as volunteers and received no compensation from the ACS. Current members are: Timothy R.
Church, PhD; Ruth Etzioni, PhD; Christopher R. Flowers, MD; Elizabeth T. H. Fontham, DrPH (Co-Chair); Carmen Guerra, MD; Samuel J. LaMonte, MD; Matthew T. McKenna, MD; Kevin C.
Oeffinger, MD (Chair); Ya-Chen Tina Shih, PhD; Louise C. Walter, MD; and Andrew M. D. Wolf, MD (Chair of the Committee Subgroup for CRC Guideline Update).

doi: 10.3322/caac.21457. Available online at cacancerjournal.com

Correction added after online publication 30 May 2018. A statement was corrected in the third paragraph of the Age to Begin CRC Screening section on page 7.

250 CA: A Cancer Journal for Clinicians

 CA CANCER J CLIN 2018;68:250–281

Introduction The detection and subsequent removal of precursor

Colorectal cancer (CRC) is the fourth most commonly
diagnosed cancer among adults in the United States.1 Over
140,000 Americans are expected to be diagnosed with CRC
in 2018. It is the second leading cause of cancer death, lead-
ing to over 50,000 deaths annually.1 CRC disease burden
varies across racial groups, with the highest incidence and
mortality rates in blacks, American Indians, and Alaska
Natives.2
Temporal trends in CRC incidence and mortality among
adults aged 55 years and older have shown a decline for sev-
eral decades that accelerated around 2000, particularly
among adults aged 65 years and older.2,3 Although changes
in exposure to risk factors account for an estimated one-half
of the reduction in incidence and one-third of the reduction
in mortality before 2000, subsequent accelerated declines in
incidence and mortality since 2000 are largely attributable
to increased uptake of screening, with improved treatment
also contributing to mortality reductions.3-6 In contrast,
among adults younger than 55 years, there was a 51%
increase in the incidence of CRC from 1994 to 2014 and an
11% increase in mortality from 2005 to 2015.7,8
Risk factors associated with a Western lifestyle that have
been shown to increase CRC risk include: cigarette smoking;
excess body weight; diet, including high consumption of
alcohol and red and processed meat and low consumption of
fruits/vegetables, dietary fiber, and dietary calcium; and
physical inactivity.9,10 Islami et al estimated that a significant
proportion of CRC incidence among women and men in
2014 (50.8% and 58.2%, respectively) was attributable to
these lifestyle factors.10 Thus, there is an important opportu-
nity to reduce risk across the population through lifestyle
modification. The use of aspirin in selected individuals has
also been demonstrated to reduce the likelihood of develop-
ing CRC.11-14 Risk for developing CRC is associated with
several identified hereditary CRC conditions; a family his-
tory of CRC15; medical conditions, including chronic
inflammatory bowel disease16 and type 2 diabetes17; and a
history of abdominal or pelvic radiation for a previous
cancer.18-21
lesions detected during screening and the detection of CRC
at an earlier, more favorable stage have been shown to sig-
nificantly reduce incidence and mortality. The increased
understanding of the natural history of CRC and precursor
lesions and the development and accumulation of evidence
on screening technologies have supported the evolution of
screening recommendations and implementation of CRC
screening in clinical practice and public health programs.22
This guideline is intended to provide guidance to adults
at average risk of CRC, to clinicians who counsel and refer
patients to CRC screening, and to health care systems to
support best practices in the early detection and prevention
of CRC. The American Cancer Society (ACS) first pub-
lished evidence-based recommendations for early detection
of cancer of the colon and rectum in 1980.23 The most
recent update of recommendations for individuals at average
risk occurred in 2008 and was based on an evidence-based
consensus process that included the ACS, the US Multi-
Society Task Force (USMSTF) on Colorectal Cancer (rep-
resenting the American College of Gastroenterology, the
American Gastroenterological Association, and the Ameri-
can Society for Gastrointestinal Endoscopy), and the Amer-
ican College of Radiology.24 Since 2008, evidence has
accumulated on the different screening modalities, test per-
formance in population-based screening programs, and the
changing risk of CRC.3,25,26 This guideline update is based
on an assessment of the underlying burden of disease; the
strength of evidence and the balance of benefits and harms
for available screening tests; and consideration of patient
values and preferences, including the importance of choice
in the selection of screening test options.
Materials and Methods
The ACS follows a protocol for developing and disseminat-
ing guidelines that is designed to maintain transparency,
consistency, and rigor.27,28 This process includes the use of
systematic evidence reviews on the topic, consideration of
the overall balance of benefits and harms of interventions
and patient preferences, a guidelines panel of scientific

Disclosures: Timothy R. Church reports grants from Epigenomics and personal fees from GRAIL Bio outside the submitted work; he is a member of the Physician’s Data Query
(PDQ) for Screening and Prevention Editorial Board (National Cancer Institute [NCI], National Institutes of Health [NIH], Chair of the CONFIRM trial Data and Safety Monitoring
Board (Veterans Affairs), site principal investigator for the Prostate, Lung, Colon, and Ovarian Cancer Screening Trial (funded by the NIH), and site principal investigator for the
National Colonoscopy Study (funded by the NIH through Memorial Sloan Kettering Cancer Center). Christopher R. Flowers reports multiple relationships with industry but none
directly related to colorectal cancer screening; personal fees from Spectrum, Celgene, Optum Rx, Seattle Genetics, Gilead, Bayer, Karyopharm, Astra Zeneca, and Beigene; unpaid
consultant work for Genentech/Biogen-Idec/Roche and Millennium/Takeda; research funding to the Emory University School of Medicine and Winship Cancer Institute from
AbbVie, Acerta, Celgene, Gilead Sciences, Infinity Pharmaceuticals, Janssen Pharmaceutical, Millennium/Takeda, Spectrum, Onyx Pharmaceuticals, Phamacyclics, and the NIH
(grants R21CA158686, U01CA195568, and K24CA208132), the Burroughs Wellcome Fund, and the V Foundation; and personal fees for developing educational presentations from
Clinical Care Options, Educational Concepts, PRIME Oncology, and Research to Practice. Otis W. Brawley and Stacey A. Fedewa are employed by the ACS, which received a grant
from Merck Inc for intramural research outside the submitted work; however, their salary is solely funded through ACS. The ACS receives partial funding from the Centers for
Disease Control and Prevention (CDC) to support the National Colorectal Cancer Roundtable, of which Richard C. Wender is the Chair, Robert C. Smith is the Co-Chair, and Durado
Brooks is a Steering Committee member, to support initiatives related to colorectal cancer screening. The ACS also received contributions from Bracco Diagnostics Inc, Polymedco
Inc, Exact Sciences, Medtronic GI Solutions Inc, Quest Diagnostics, Epigenomics Inc, Clinical Genomics, Medial Early Sign, the American Society for Gastrointestinal Endoscopy, the
American College of Gastroenterology, the American College of Radiology, and the American Gastroenterological Association to support the annual meeting of the National Colorec-
tal Cancer Roundtable. ACS cancer screening guideline development is supported by ACS operational funds; neither the Roundtables nor the sources of funding described in this
disclosure have had any role, involvement, or have made any financial contribution to ACS screening guideline development or approval. All remaining authors report no conflicts of
interest.

VOLUME 68 _ NUMBER 4 _ JULY/AUGUST 2018 251

 ACS Colorectal Cancer Screening Guideline
experts without any direct professional specialization in the
issue under review, a transparent disclosure and manage-
ment process that minimize biases and conflicts of interest,
explicit explanation of the logical relationships between
screening interventions and health outcomes, and ratings of
both the quality of evidence and the strength of the
recommendations.
The ACS Guideline Development Group (GDG), a
multidisciplinary panel of volunteers comprising generalist
clinicians, biostatisticians, epidemiologists, economists, and
a patient representative, is charged with the development
and update of the ACS cancer screening guidelines. The
GDG has full responsibility for interpretation of the evi-
dence, formulating the recommendations, deliberation and
voting on the recommendations and strength, and writing
the guideline. A record of voting on the recommendations
is kept without attribution. While the GDG attempts to
achieve complete agreement, a three-quarters majority is
considered acceptable for adopting a recommendation and
assigning strength. For the update of the CRC screening
guideline, a subcommittee consisting of 6 GDG members
had primary responsibility for reviewing the evidence, draft-
ing recommendations, and preparing the manuscript for
publication, although the entire GDG reviewed and voted
on the updated guideline. ACS staff members served as
guideline methodologists and in an administrative capacity
to support the GDG. ACS staff members also contributed
cancer screening and CRC expertise to the GDG evaluation
of the evidence and participated in preparation of the manu-
script but did not formulate recommendations or vote to
approve the final guideline. Guideline development is sup-
ported by ACS general operating funds.
Individuals with recognized clinical and research expertise
in the areas of CRC natural history, detection, diagnosis,
and decision making were invited to advise the GDG and
to provide broader knowledge and understanding of the
complexity of CRC screening (see Supporting Information).
The GDG consulted the expert advisors at several stages in
the guideline development process: the expert advisors were
requested to respond to questions about the key evidence
questions and the evidence and logic underlying screening
recommendations and to assess the primary evidence reports
and suggest additional data for consideration. In addition,
they served as external reviewers of the draft recommenda-
tion statements and the guideline manuscript before
publication.
Participants (GDG members, ACS staff, expert advisors)
in all stages of the guideline development process were
required to disclose all financial and nonfinancial (personal,
intellectual, practice-related) relationships and activities that
might be perceived as posing a conflict of interest in the
update of the CRC screening guideline. The GDG
252 CA: A Cancer Journal for Clinicians
chairpersons had the responsibility to ensure balanced per-
spectives were considered in deliberations and decision
making.
For the update of the CRC screening guideline, the
GDG chose to use 2 reports commissioned by the US
Preventive Services Task Force (USPSTF) for its 2016
CRC screening recommendation update as sources of evi-
dence to inform recommendations: a systematic evidence
review on CRC screening and a report of simulation model-
ing findings from the Cancer Intervention and Surveillance
Modeling Network (CISNET) CRC group.26,29-31 The
evidence synthesis conducted for the USPSTF addressed 3
issues: the effectiveness of screening in reducing incidence
and mortality from CRC, the test performance characteris-
tics of different screening tests for detecting CRC and
important precursor lesions, and the adverse effects associ-
ated with different screening tests. Three microsimulation
models of CRC screening developed as part of the CISNET
consortium estimated the impact of a variety of program-
matic screening strategies for the screening-eligible US pop-
ulation. The CISNET-CRC group consists of 3 CRC
microsimulation models that were independently developed
for the evaluation of interventions, and their use to date
principally has focused on screening. The 3 models differ
somewhat in their underlying assumptions about the natural
history of CRC, which allows for estimation of outcomes
based on these different assumptions. The CISNET-CRC
models include: 1) MISCAN-CRC, with investigators
from Erasmus University Medical Center and Memorial
Sloan Kettering Cancer Center; 2) SimCRC from the Uni-
versity of Minnesota and Massachusetts General Hospital;
and 3) CRC-SPIN from RAND Corporation.32
To gain additional understanding of outcomes associated
with different screening strategies (particularly starting age)
for black and white adults, the ACS commissioned a model-
ing study by the MISCAN and SimCRC investigators (2 of
the CISNET modeling groups) that extended the previous
analysis conducted for the USPSTF. The objective was to
assess the potential benefit (life-years gained and CRC
deaths averted) and the burden of different CRC screening
strategies for black and white women and men.33 Subse-
quently, the GDG determined that recent evidence demon-
strating a significant increase in CRC incidence among
individuals younger than 55 years, which was attributable to
a strong birth-cohort effect,3 warranted a reevaluation of
the optimal age to start screening in the average-risk popu-
lation. Additional modeling analyses by the MISCAN
investigators incorporated recent Surveillance, Epidemiol-
ogy, and End Results (SEER) incidence data and evaluated
screening outcomes for the general US population.34 Analy-
ses of outcomes for race-specific and sex-specific groups by
MISCAN and SimCRC, which initially were carried out

under the assumption of stable incidence, were repeated to
incorporate recent SEER incidence data.33
Under the direction of the GDG, the ACS staff per-
formed a supplemental literature review to examine differ-
ential risk and screening outcomes in racial and ethnic
subgroups. In addition, literature searches were conducted
to identify relevant new studies that have addressed screen-
ing outcomes since completion of the USPSTF evidence
review. The GDG also examined data provided by the ACS
Surveillance and Health Services Research Program on dis-
ease burden using data from the SEER program.35 Unless
otherwise indicated, all incidence and mortality rates are per
100,000 person-years and age-adjusted to the US standard
population.
While the primary source of evidence for this guideline
used a different rating system for the appraisal of evi-
dence,26,29 the GDG applied the principles of the Grades of
Recommendations, Assessment, Development, and Evalua-
tion (GRADE) and GRADE Evidence-to-Decision (EtD)
frameworks in formulating and assigning the strength of rec-
ommendations.36,37 The principal GRADE decision-making
criteria are: 1) balance between desirable and undesirable
effects—the greater the difference between desirable and
undesirable effects, the higher the likelihood that a strong rec-
ommendation is warranted, and the narrower the difference,
the higher the likelihood that a qualified recommendation is
warranted; 2) quality of evidence—the higher the quality of
evidence, the higher the likelihood that a strong recommen-
dation is warranted; and 3) values and preferences—the
greater the uniformity or certainty in values and preferences,
the higher the likelihood that a strong recommendation is
warranted. Each recommendation was designated by the
GDG as either strong or qualified, in accordance with
GRADE guidance.38 A strong recommendation conveys the
consensus that the benefits of adherence to the intervention
outweigh the undesirable effects and that most patients would
choose the intervention. A qualified recommendation indi-
cates there is clear evidence of benefit (or harm) but less cer-
tainty either about the balance of benefits and harms or about
patients’ values and preferences, which could lead to different
individual decisions. Additional elements included in the
GRADE EtD framework and considered in this guideline
are the impact on health equity, feasibility, and acceptability.37
The ACS does not apply cost and resource use as a decision-
making criterion for recommendations. Actual costs of CRC
screening tests and follow-up examinations vary widely in the
United States, and costs, coverage, and reimbursement may
be important considerations for individuals when making
decisions about screening tests (see Patient considerations of
cost and reimbursement, below).
Before final preparation of a manuscript for publication,
the guideline was submitted to the ACS Mission Outcomes
CA CANCER J CLIN 2018;68:250–281
Committee and Board of Directors for review and approval
of the proposed recommendations. The expert advisors and
representatives from 30 relevant outside organizations were
then invited to participate in an external review of the
guideline. Responses were documented and reviewed by the
GDG to determine whether modifications in the recom-
mendations or narrative were warranted, and adopted
changes were incorporated in the final manuscript.
Considerations in Developing
Recommendations
Outcomes of Screening
The GDG identified reduction in CRC mortality (mea-
sured as life-years gained [LYGs] in the modeling reports)
and incidence as the principal benefits of screening.
Although the previous ACS guideline gave priority to CRC
incidence reduction, in this update, the GDG did not prior-
itize incidence reduction over mortality reduction. There is
variability in prevention potential among the available
screening tests, but all noncolonoscopy screening tests con-
tribute to prevention through colonoscopy follow-up and
adenoma removal after a positive initial screening test, as
demonstrated by the reduction in incidence in the US
guaiac fecal occult blood test (gFOBT) randomized trial.39
Although prevention is highly valued by patients, test prep-
aration, invasiveness, potential costs, and other consider-
ations will lead some patients to prefer a noncolonoscopy
test for screening. Greater value was placed on the role of
patient preferences and on the potential to increase CRC
screening utilization through offering choice in screening
test options. The GDG recognized the potential relevance
of other beneficial outcomes, including reduction of disease
and treatment morbidity and improved quality of life, but
identified no studies that demonstrated direct associations
with screening.
The principal recognized harms of CRC screening, which
are rare, are those associated with colonoscopy (bleeding,
perforation, cardiorespiratory complications of sedation) as
a primary screening test or as a follow-up of other positive
noncolonoscopy tests.26,40,41 The harm conventionally asso-
ciated with workup of false-positive test results is partly mit-
igated when a normal follow-up examination removes the
patient from the screening pool for 10 years. In addition to
estimating the number of colonoscopy-related complica-
tions, the CISNET modeling group used the number of
colonoscopies required as a proxy for harms and a measure
of the burden of CRC screening.30 The GDG regarded the
number of colonoscopies (and related risk of complications)
as a proxy for harms. Individual patient burden was consid-
ered primarily in the context of patient decision making on
the basis of test attributes. For computed tomography colo-
nography (CTC), attention was given to additional
VOLUME 68 _ NUMBER 4 _ JULY/AUGUST 2018 253
 ACS Colorectal Cancer Screening Guideline
potential harms associated with radiation exposure and
workup of incidental findings not leading to residual benefit.
Screening test performance measures (sensitivity, specificity,
etc) were included as important outcomes in evaluating the
evidence on screening tests. Relatively low importance was
ascribed to the beneficial effect of reassurance from a nega-
tive screening test as well as to the burden of anxiety precip-
itated by a false-positive test result.
Evidence-Based Inferential Reasoning
Results from randomized controlled trials (RCTs) of CRC
screening with either a stool-based test (gFOBT) or a struc-
tural examination (flexible sigmoidoscopy [FS]) have dem-
onstrated mortality reductions associated with the detection
of advanced neoplasia in asymptomatic adults.26 The evi-
dence of benefit for all other screening tests is limited to test
performance data demonstrating the ability to detect early
stage CRC and/or advanced adenomas and observational
studies. In addition to this body of evidence for the individ-
ual modalities, the GDG adopted evidence-based inferential
reasoning to extrapolate from the evidence establishing a
rationale for using the detection of occult blood as an effec-
tive screening tool to support fecal immunochemical testing
(FIT) and multitarget stool DNA (mt-sDNA) testing,
which includes multiple molecular assays combined with a
hemoglobin immunoassay. Similarly, findings from RCTs
of FS provide a compelling “proof of concept” for structural
evaluation of the colon to detect both CRC and adenomas
as an effective approach to reducing CRC incidence and
mortality. In addition to examining the test performance
and observational data on the other 2 currently available
structural examinations (colonoscopy and CTC), the GDG
made the judgment to extrapolate the RCT evidence on FS.
Use of Modeling Studies
Given the limited evidence on long-term outcomes for the
different screening options as well as direct comparisons,
modeling studies have been used to compare the potential
effectiveness of different screening strategies, and the
results of these studies have influenced the USPSTF CRC
screening recommendations.30,42-44 The CISNET investi-
gators have devised a methodology to identify model-
recommended screening strategies for consideration
among the numerous unique strategies that are generated
by combinations of tests with different starting and stop-
ping ages and screening intervals.
Model-recommended screening strategies for individual
tests are based on the balance of benefits, expressed as
LYGs (corrected for life-years lost because of screening
complications) versus burden and harms, expressed as the
number of colonoscopies required for a given strategy
(screening, follow-up, surveillance, and diagnosis of
254 CA: A Cancer Journal for Clinicians
symptomatic cancer). The burden of noncolonoscopy tests is
addressed by grouping and comparing screening options
that have similar test characteristics, resulting in 4 separate
classes of screening tests (ie, colonoscopy, all stool tests, FS,
and CTC). Strategies within each class that achieve the
highest LYGs for a given number of colonoscopies are
deemed efficient, whereas strategies that achieve at least
98% of the highest LYGs are deemed “near-efficient.” For
all efficient and near-efficient strategies, an efficiency ratio
(ER) is estimated, which is a measure of burden to benefit
based on the ratio of the incremental number of colonosco-
pies divided by the incremental number of LYGs compared
with the nearest less effective efficient strategy. From the
efficient or near-efficient strategies in each class, model-
recommendable strategies are those that have an acceptable
overall benefit and ER (balance of burden to benefit).33,34
The limitations of modeling arise from the uncertainty
inherent in the parameters and assumptions that underpin
the model inputs. One such assumption in the CISNET
models30,31 is 100% adherence to all screening strategies,
including 100% adherence to follow-up colonoscopy for
positive initial noncolonoscopic screening examinations.
The assumption of full adherence allows for comparison of
the screening options under a uniform scenario. However,
actual screening and follow-up adherence rates vary by test,
setting, and population group, meaning that actual out-
comes could diverge from predicted outcomes based on dif-
ferential uptake and follow-up. These limitations are
acknowledged by the CISNET investigators and were
acknowledged by the GDG in integrating modeling results
with empirical evidence.
Patient Preferences, Choice, and Adherence
CRC screening presents a unique challenge and opportu-
nity, as there are multiple screening tests with variability in
supporting evidence of effectiveness, risk of harm, preven-
tion potential, and patient burden. There is no consistent,
direct evidence that adults prefer any one CRC screening
tool or strategy over others. Individual preferences can be
influenced by patient education about screening, test charac-
teristics (ie, accuracy, degree of invasiveness, test prepara-
tion, required screening interval, and cost), and clinician
recommendation.45-50 The ACS is committed to increasing
utilization to achieve the benefits of CRC screening by rec-
ommending that patients be given an opportunity to choose
a testing strategy, thus increasing the likelihood of adher-
ence. Patient preference is an important consideration,
although the choice of test must be predicated on high-
quality screening test options that are accessible to the
patient, and there must be access to follow-up colonoscopy
if needed.
 CA CANCER J CLIN 2018;68:250–281

TABLE 1. American Cancer Society Guideline for CRC Screening, 2018

Recommendationsa
The ACS recommends that adults aged 45 y and older with an average riskb of CRC undergo regular screening with either a high-sensitivity stool-based test or
a structural (visual) examination, depending on patient preference and test availability. As a part of the screening process, all positive results on noncolonoscopy
screening tests should be followed up with timely colonoscopy.
The recommendation to begin screening at age 45 y is a qualified recommendation.
The recommendation for regular screening in adults aged 50 y and older is a strong recommendation.
The ACS recommends that average-risk adults in good health with a life expectancy of greater than 10 y continue CRC screening through the age of 75 y
(qualified recommendation).
The ACS recommends that clinicians individualize CRC screening decisions for individuals aged 76 through 85 y based on patient preferences, life expectancy,
health status, and prior screening history (qualified recommendation).
The ACS recommends that clinicians discourage individuals over age 85 y from continuing CRC screening (qualified recommendation).
Options for CRC screening
Stool-based tests
l Fecal immunochemical test every y
l High-sensitivity, guaiac-based fecal occult blood test every y
l Multitarget stool DNA test every 3 y
Structural examinations
l Colonoscopy every 10 y
l CT colonography every 5 y
l Flexible sigmoidoscopy every 5 y

ACS, American Cancer Society; CRC, colorectal cancer; CT, computed tomography. aA strong recommendation conveys the consensus that the benefits of
adherence to that intervention outweigh the undesirable effects that may result from screening. Qualified recommendations indicate there is clear evi-
dence of benefit (or harm) of screening but less certainty about the balance of benefits and harms or about patients’ values and preferences, which could
lead to different decisions about screening. bThese recommendations represent guidance from the ACS for persons without a history of adenomatous pol-
yps or CRC and not at increased risk for CRC due to a family history of CRC, a confirmed or suspected hereditary CRC syndrome (such as familial adeno-
matous polyposis or Lynch syndrome), a personal history of abdominal or pelvic radiation for a previous cancer, or a personal history of inflammatory
bowel disease.

Recommendations recommendations for the use of specific individual tests.

The ACS recommends that adults aged 45 years and
older with an average risk of colorectal cancer undergo
regular screening with either a high-sensitivity stool-
based test or a structural (visual) examination, depending
on patient preference and test availability. As a part of
the screening process, all positive results on noncolono-
scopy screening tests should be followed up with timely
colonoscopy. The recommendation to begin screening at
age 45 years is a qualified recommendation. The recom-
mendation for regular screening in adults aged 50 years
and older is a strong recommendation (Table 1).
This recommendation for CRC screening in average-
risk adults is based on the GDG’s judgment of the pre-
ponderance of benefits of CRC screening over harms, the
overall quality of the evidence on screening outcomes,
recent evidence related to the incidence of disease, evi-
dence demonstrating the influence of test preference on
adherence to recommendations, and the high value indi-
viduals place on preventing and avoiding death from
CRC.51,52 The GDG chose to issue a general overall
recommendation for CRC screening rather than
Although there is significant variability among the avail-
able screening tests in the volume and quality of support-
ing evidence, the overall quality of the evidence was
judged to be good and sufficient to support a recommen-
dation for screening with any of the 6 included strategies
(Table 1). On the basis of the strength of the evidence and
on the judgment of an overall preponderance of benefit,
the recommendation for regular screening in adults aged
50 years and older has been designated as a “strong” rec-
ommendation. The recommendation to begin screening at
age 45 years is based on disease burden, results from
microsimulation modeling, and the reasonable expectation
that screening will perform similarly in adults aged 45 to
49 years as in persons for whom screening is currently rec-
ommended. However, the long-standing recommendation
to initiate CRC screening at age 50 years means that there
are limited data on screening outcomes in adults aged 45
to 49 years. Because of differences in the type and quality
of evidence for screening in adults younger than 50 years,
as described below, the recommendation to start screening
at age 45 years has been designated as “qualified.”

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 ACS Colorectal Cancer Screening Guideline
Age to Begin CRC Screening
Burden of disease
When initiating this guideline update and examining the
burden of disease, the GDG initially focused on higher
than average incidence before age 50 years in some racial
subgroups.35,53 Beginning screening earlier in these groups
would be consistent with a disease burden approach and
could contribute to reducing disparities.2,54,55 Some organi-
zations already have recommended that blacks and Alaska
Natives begin screening before age 50 years based on their
higher incidence at younger ages.56-58 However, prior
reports showing the persistence of a trend of increasing
CRC incidence in adults younger than 50 years59-62 and the
recent work by Siegel et al3 demonstrating that this rising
incidence was the result of a strong birth-cohort effect that
would carry forward with age led the GDG to reevaluate
the age to initiate screening in all US adults.
CRC incidence rates in the United States have historically
varied by sex as well as by race and ethnicity. Among all races
combined, CRC incidence is similar in women and men
until age 35 years but, thereafter, is higher for men, and the
disparity widens with age. CRC incidence among blacks,
including those younger than 50 years, has historically been
higher than that among whites, Hispanics, and Asian Amer-
icans.2 However, while incidence rates in whites younger
than 50 years have risen, incidence rates for blacks younger
than 50 years have remained generally stable, resulting in
comparable contemporary incidence between the 2 groups
(Fig. 1). The CRC incidence rate for individuals younger
than 50 years is higher among Alaska Natives than for any
other racial/ethnic group in the United States.2,63 High rates
have been reported for some American Indian groups,
although this varies by tribe and geographic region.64
CRC incidence has declined steadily over the past 2 decades
in the population aged 50 years and older because of the com-
bined influence of screening and changes in exposure to risk fac-
tors,4 but there has been about a 51% increase in CRC among
those younger than 50 years since 1994 (Fig. 2). Increased inci-
dence rates have been particularly notable for rectal cancer,
which doubled between 1991 (2.6 of 100,000) and 2014 (5.2 of
100,000) in individuals aged 20 to 49 years.7 A recent analysis
found that adults born around 1990 have twice the risk of colon
cancer and 4 times the risk of rectal cancer compared with adults
born around 1950, who have the lowest risk.3
The factors contributing to this increase in incidence are
not understood.2,3 The increase in incidence observed in the
youngest birth cohorts is not likely due to detection bias
arising from increased use of colonoscopy, because negligi-
ble screening and case finding occur in the youngest cohorts,
and the increased incidence in whites is accompanied by an
increase in mortality, which is contrary to what would be
expected if increased incidence in this group was because of
256 CA: A Cancer Journal for Clinicians
16
Colorectal cancer cases per 100,000 persons <50years
14
12
10
8
6
4
2
White Black
0
Year or diagnosis
FIGURE 1. Trends in Colorectal Cancer Incidence Rates in Adults Younger
Than Age 50 Years by Race, 1975 to 2014.
increased screening.3 The observation that CRC incidence
is increasing in successively younger birth cohorts suggests
that the greater burden of CRC in the population younger
than 50 years is not just a transient epidemiological phe-
nomenon. Rather, these birth cohorts are carrying the ele-
vated risk with them as they age; increases in colon cancer
incidence began in the mid-1980s and have continued
through 2013 for the groups aged 20 to 29 years (2.4% per
year) and aged 30 to 39 years (1% per year) and in the mid-
1990s for the groups aged 40 to 49 years (1.3% per year)
and 50 to 54 years (0.5% per year). Rectal cancer incidence
rates increased 3.2% per year from 1974 to 2013 in adults
aged 20 to 29 years, 3.2% per year from 1980 to 2013 in
adults aged 30 to 39 years, and 2.3% per year from the early
to mid-1990s to 2013 in adults aged 40 to 54 years.3 Siegel
et al also noted a recent convergence of CRC incidence rates
in the groups aged 50 to 54 years and 55 to 59 years (Fig.
3); in the early 1990s CRC incidence rates in adults aged 50
to 54 years were one-half of those in the group aged 55 to
59 years, whereas in 2012-2013 there was just a 12.4% dif-
ference in colon cancer rates, and rectal cancer rates were
the same for the 2 age groups.3 This rising incidence in
younger age groups coinciding with rapid declines in older
age groups has led to a large shift in the age-adjusted pro-
portion of CRC in adults younger than 55 years, from
11.6% during 1989 to 1990 to 16.6% during 2012 to 2013
for colon tumors and from 14.6% to 29.2%, respectively, for
rectal tumors.3
Although the current age-specific incidence rate among
adults aged 45 to 49 years (31.4 per 100,000) is lower com-
pared with that among adults aged 50 to 54 years (58.4 per
100,000),35 the higher rate in the group aged 50 to 54 years
is influenced by lead time associated with the uptake of
screening as well as rising incidence because of increasing
age. Data from the National Health Interview Survey
revealed that approximately 45.3% of adults aged 50 to 54
years reported recent screening with either colonoscopy or
 CA CANCER J CLIN 2018;68:250–281

14

Colorectal cancer cases per 100,000 persons

Men
12

10
Women

aged 20-49 years

8

Year of diagnosis

300
Colorectal cancer cases per 100,000 persons aged

250

200
Men
150
50+ years

Women
100

50

Year of diagnosis
FIGURE 2. Trends in Colorectal Cancer Incidence Rates by Age (Ages 20-49 and Ages 501) and Sex, 1975 to 2014. Rates are adjusted for delays in report-
ing and are plotted as a 2-year moving average. Data source: Surveillance, Epidemiology, and End Results program, National Cancer Institute, 2017.

FS in 2015 compared with approximately 17.8% of adults
aged 40 to 49 years.65 Thus, the true underlying risk in
adults aged 45 to 49 years is likely closer to the risk in adults
aged 50 to 54 years than the most recent age-specific rates
would suggest. More noteworthy, however, is that the
increase in the annual percentage change in the incidence
rate for adults aged 40 to 49 years (1.3%) is more than twice
that of adults aged 50 to 54 years (0.5%), suggesting that
the risk for the younger cohort will continue to carry for-
ward into the group aged 50 to 54 years.3
Although the data described above pertain to trends in
the risk of invasive disease, Lieberman et al reported that
the prevalence of polyps measuring 9 mm or greater
among adults younger than 50 years was 4.2% in whites
and 6.2% in blacks, similar to the prevalence of 5.3% in
whites and 6.1% in blacks aged 50 to 59 years.66 Insofar
as prevention also is a goal of CRC screening, these data
indicating a similar prevalence of large polyps in adults
aged 45 to 49 years and 50 to 54 years point to the disease
prevention potential of beginning screening at age 45
years.
Further confirmation of a change in underlying disease
risk is the increase in CRC mortality among white adults
aged 50 to 54 years since 2005, after decades of decline
in an age group in which screening is recommended.3
CRC mortality rates have been increasing since 1995 in
whites aged 30 to 39 years and since 2005 in whites aged
40 to 54 years. In contrast, mortality rates have been
decreasing since 1970 among blacks aged 20 to 54 years
but still were about 50% higher compared with the rates
among whites in this age group in 2014 (6.1 vs 4.1 per
100,000).
It is further noteworthy that, of all CRC deaths during
2010 through 2014, a similar proportion of decedents
were diagnosed at ages 45 to 49 years (5.1%) compared
with ages 50 to 54 years (7.6%) (Fig. 4A). Likewise, of all
estimated premature mortality from the disease measured
by years of potential lives lost, 10% was because of diag-
noses in persons aged 45 to 49 years compared with 13%
attributable to diagnoses in those aged 50 to 54 years
(Fig. 4B).
Evidence of the effectiveness of screening in adults
aged 45 to 49 years
There is limited direct evidence of screening effectiveness in
adults younger than 50 years, in large part because of early

VOLUME 68 _ NUMBER 4 _ JULY/AUGUST 2018 257

 ACS Colorectal Cancer Screening Guideline
FIGURE 3. Trends in Colorectal Cancer Incidence Rates by Age and Year of Birth, and by Age and Year of Diagnosis, United States, 1975 to 2014.
Data source: Surveillance, Epidemiology, and End Results (SEER) program, SEER 9 registries, delayed adjusted rates, 1975-2014, National Cancer
Institute.
expert judgments, based on disease burden, that screening
should begin at age 50 years.23,67,68 Most of the RCTs of
CRC screening demonstrating benefit had a starting age of
50 years, as do the RCTs of colonoscopy/FIT25,69 and
CTC/colonoscopy/FIT/FS70-72 that are currently in pro-
gress. Three of the European gFOBT trials conducted in
the 1980s and 1990s that demonstrated a CRC mortality
benefit enrolled persons starting at age 45 years (45-74 years
or 75 years).26 However, all were underpowered for age sub-
group analyses, and age-specific outcomes were not
reported. Much of the observational evidence demonstrating
effectiveness of CRC screening is similarly limited to a
starting age of 50 years.
Modeling Analyses
Given the limited empirical data on long-term screening
outcomes across screening modalities and strategies and the
paucity of comparative data, recommendations for CRC
screening over the past decade increasingly have relied on
modeling analyses of screening outcomes.30,42 It should be
258 CA: A Cancer Journal for Clinicians
noted that the modeling report prepared for the USPSTF
2016 CRC screening recommendations determined that,
“for all modalities, strategies with screening beginning at
age 45 years predominated on the efficient frontier; that is,
these strategies generally provided additional LYGs at a
lower number of additional colonoscopies than strategies
with screening beginning at later ages.”30 However, begin-
ning screening at age 45 years while maintaining the
10-year screening interval, resulted in an increase in the esti-
mated lifetime number of colonoscopies. In 2 models
(SimCRC and CRC-SPIN), starting screening at age 45
years but extending the screening interval to 15 years
resulted in slightly more LYGs and a similar lifetime num-
ber of colonoscopies compared with screening with colonos-
copy every 10 years from aged 50 to 75 years.30 Ultimately,
the USPSTF elected not to recommend the younger start-
ing age, judging that the estimated additional LYGs would
be “modest,” also noting that 1 of the 3 models in the 2016
report (the MISCAN model) did not corroborate the mod-
est increase in LYGs associated with the younger starting
 CA CANCER J CLIN 2018;68:250–281

A
85+ years
80-84 years
75-79 years
70-74 years
65-69 years
Age at diagnosis
60-64 years
55-59 years
50-54 years
45-49 years
40-44 years
35-39 years
30-34 years
25-29 years
20-24 years
0.0 2.0 4.0 6.0 8.0 10.0 12.0 14.0 16.0 18.0
Percentage

B 85+ years
80-84 years
75-79 years
Age at diagnosis

70-74 years
65-69 years
60-64 years
55-59 years
50-54 years
45-49 years
40-44 years
35-39 years
30-34 years
0.0 2.0 4.0 6.0 8.0 10.0 12.0 14.0 16.0
Percentage
FIGURE 4. Distribution of Colorectal Cancer Burden by Age at Diagnosis, 2010 to 2014. (A) The distribution of colorectal cancer (CRC) deaths by age
at diagnosis (n 5 20,198) is illustrated among patients who were followed for 20 years after diagnosis. (B) The distribution of person-years of life lost
(YLL) because of CRC by age at diagnosis is illustrated among patients who were followed for 20 years after diagnosis. Source: SEER 9 registries.

age and a 15-year screening interval, and citing the lack of
empirical evidence for screening younger populations and a
15-year screening interval.44
The CISNET modeling analyses used for the 2016
USPSTF update were based on historical CRC incidence
data from the prescreening era (1975-1979) to reflect risk
without the influence of screening on incidence (prevention
and early detection). Although this was a reasonable meth-
odological decision, the model outputs did not reflect
changes in incidence because of underlying changes in risk
that may have occurred over time. On the basis of the recent
trends in CRC incidence before age 55 years described pre-
viously3 and the higher burden of disease in blacks com-
pared with whites, the ACS worked with 2 of the CISNET
groups (MISCAN and SimCRC) to reexamine optimal
screening strategies, with emphasis on the influence of
observed trends in incidence on the age to begin screening.
Outcomes of different screening strategies were predicted
for the general population under the increased-risk scenario
(MISCAN only)34 and for population subgroups defined by
race and sex under both the stable-risk scenario and the
increased-risk scenario (MISCAN and SimCRC models).33
With respect to the reevaluation of screening strategies
for the general population with emphasis on observed trends
in incidence, the analyses were similar to those carried out
for the USPSTF, with the principal exception of the appli-
cation of incidence multipliers to adjust risk proportional to
the observed increase in incidence in adults younger than 40
years (to rule out any potential contamination from screen-
ing). The models also accounted for the higher proportion
of tumors in the rectum and distal colon observed in the
incidence trends among younger adults.3 This adjustment in
risk was based on the observation that increased incidence
in adults younger than 55 years is attributable to a strong
birth-cohort effect that began in the 1950s and is carrying
over as these cohorts age. Six screening modalities (colonos-
copy, CTC, FS, mt-sDNA, FIT, and high-sensitivity
gFOBT [HSgFOBT]) were evaluated with variation in the
starting age (40, 45, and 50 years), ending age (70, 75, and
80 years), and screening intervals, which varied by screening
test, for a total of 132 unique CRC screening strategies.
Among 9 efficient and 5 near-efficient colonoscopy strat-
egies, the strategy recommended by the model under the
increased-risk scenario was screening every 10 years from

VOLUME 68 _ NUMBER 4 _ JULY/AUGUST 2018 259

 ACS Colorectal Cancer Screening Guideline

500

450

400
Model-estimated LYG

350

300

250

200

150

100

50

0
CSY CTC FS FIT HSgFOBT mt-sDNA
Screening test

LYG 45y-75y LYG 50y-75 y

FIGURE 5. Model-Estimated Life-Years Gained (LYG) from Colorectal Cancer Screening Starting at Age 45 Years Versus 50 Years, per 1000 Screened
Over a Lifetime. CSY indicates colonoscopy; CTC, computed tomography colonography; FSIG, flexible sigmoidoscopy; FIT, fecal immunochemical test;
gFOBT, guaiac-based fecal occult blood test; LYG, life-years gained; mt-sDNA, multitarget stool DNA. Adapted from: Peterse EFP, Meester RGS, Siegal
RL, et al. The impact of the rising colorectal cancer incidence in young adults on the optimal age to start screening: microsimulation analysis I to inform
the American Cancer Society colorectal cancer screening guideline. Cancer. 10.1002/cncr.31543 [epub ahead of print].34

ages 45 to 75 years, which, compared with screening every microsimulation models support the conclusion that starting
10 years from ages 50 to 75 years, had 6.2% more LYGs screening at age 45 years is an efficient and recommendable
and 17% more colonoscopies per 1000 adults over a lifetime strategy for the general population.
of screening (Fig. 5).34 This strategy was chosen as the
benchmark strategy because it had the highest LYGs among
strategies with ERs less than a predetermined benchmark.
Other model-recommended strategies for adults aged 45 to TABLE 2. Model-Estimated Benefits and Burdens of CRC
75 years under the increased-risk scenario included annual Screening Starting at Age 45 Versus 50 Years,
FIT, CTC every 5 years, and FS every 5 years (Table 2).34 per 1000 Screened Over a Lifetime
In the analysis of race-specific and sex-specific strategies, MODEL
using 2 CISNET models, CRC screening was evaluated SCREENING TEST LYG NO. OF CSY RECOMMENDABLE

under both stable-risk and increased-risk scenarios. For the CSY every 10 y, 45-75 429 5646 Yes
analyses in which prescreening era incidence data were used CSY every 10 y, 50-75 404 4836 No
to reflect risk (stable-risk scenario), both models concluded CTC every 5 y, 45-75 390 2666 Yes
that colonoscopy screening from ages 45 to 75 years was rec-
CTC every 5 y, 50-75 368 2430 No
ommendable for black women and men, although the MIS-
FSIG every 5 y, 45-75 403 3761 Yes
CAN model recommended a 10-year interval, and the
SimCRC model recommended a 15-year interval.33 For FSIG every 5 y, 50-75 380 3426 No

whites, the SimCRC model recommended the same strategy FIT yearly, 45-75 403 2698 Yes
that was recommended for blacks, while the MISCAN FIT yearly, 50-75 377 2402 No
model recommended colonoscopy from ages 50 to 75 years HSgFOBT yearly, 45-75 403 3364 No
every 10 years. When the models were adjusted for increased HSgFOBT yearly, 50-75 377 2956 No
incidence, both models recommended screening strategies
mt-sDNA every 3 y, 45-75 376 2640 No
from ages 45 to 75 years (colonoscopy every 10 years, FIT
mt-sDNA every 3 y, 50-75 350 2331 No
annually, FS every 5 years, and CTC every 5 years) for both
black women and men and white women. For white men CRC, colorectal cancer; CSY, colonoscopy; CTC, computed tomography colo-
nography; FIT, fecal immunochemical test; FSIG, flexible sigmoidoscopy;
aged 45 to 75 years, the SimCRC recommended these same HSgFOBT, high-sensitivity, guaiac-based fecal occult blood test; LYG, life-
strategies, while the MISCAN model only recommended years gained; mt-sDNA, multitarget stool DNA. Adapted from: Peterse EFP,
Meester RGS, Siegel RL, et al. The impact of the rising colorectal cancer inci-
screening with colonoscopy every 5 years.33 Thus, under the dence in young adults on the optimal age to start screening: microsimulation
increased-risk scenario, both overall and race-specific and analysis I to inform the American Cancer Society colorectal cancer screening
guideline. Cancer. 10.1002/cncr.31543 [epub ahead of print].34
sex-specific analyses33,34 by the 2 independent

260 CA: A Cancer Journal for Clinicians


The MISCAN analyses for the general population also
evaluated strategies starting screening at age 40 years.
Results indicated a small increase in the number of LYGs
(438 vs 429), with the same number of deaths averted (37)
per 1000 adults, for colonoscopy every 10 years with a start-
ing age of 40 years compared with 45 years.34 The incre-
mental burden of additional colonoscopies resulted in an
ER for this strategy above 45, which is higher than the
model-recommended strategy for starting screening at age
45 years. The incidence of CRC in adults aged 40 to 44
years is 17.6 per 100,000 versus 31.4 per 100,000 for adults
aged 45 to 49 years (58.4 per 100,000 for adults aged 50-54
years).35 Because of lower incidence, the years of life lost
because of CRC among persons diagnosed at ages 40 to 44
years are measurably less than in the group ages 45 to 49
years (6% vs 10% of total years of potential lives lost) and
well below those in the older age groups for whom screening
is currently recommended (Fig. 4B). Trends in incidence
and mortality in adults younger than 50 years and accumu-
lating evidence on screening performance in younger popu-
lations will continue to be monitored and will be examined
in future guideline updates.
As noted above, microsimulation modeling conducted to
inform the 2016 update of the USPSTF CRC screening
recommendations found that screening strategies beginning
at age 45 years provided additional LYGs at a lower number
of additional colonoscopies than strategies that began
screening at a later age.30 The analyses conducted for the
2018 ACS update address the principal concerns raised by
the USPSTF in choosing not to recommend a younger
starting age. First, the modeling analyses conducted for this
update incorporating an increased-risk scenario provide
stronger support for beginning screening at age 45
years.33,34 When the MISCAN model, which was the non-
concordant model in the 2016 analysis, was adjusted to
reflect increased incidence, screening beginning at age 45
years had a favorable balance of benefit to colonoscopy bur-
den for all adults, and there was an improvement in LYGs
compared with starting screening at age 50 years.33,34 Sec-
ond, although SimCRC still indicates that colonoscopy
screening every 15 years is recommended under the stable-
risk scenario, which was not corroborated by MISCAN,
there was concordance between the 2 models on a 10-year
interval under the increased-risk scenario.33
Summary: Age to begin screening
Although there is little evidence on screening outcomes in
adults aged 45 to 49 years, observational studies suggest that
both structural and stool-based CRC screening tests per-
form similarly in cancer and adenoma detection among
individuals younger than 50 years and among older individ-
uals.73-75 The GDG acknowledged that the absolute benefit
expected from screening in adults aged 45 to 49 years was
CA CANCER J CLIN 2018;68:250–281
lower than that in other age groups for which screening is
currently recommended but judged that the tradeoff
between reduced CRC mortality and incidence and
increased number of colonoscopies was favorable.
The GDG considered other factors in formulating its
recommendation for the age to start screening. First, the
potential harms of colonoscopy (as either a primary screen-
ing or follow-up examination) are lower in younger versus
older adults.40 Second, recent estimates indicate that the
current colonoscopy capacity in the United States should be
able to accommodate the anticipated increase in colonosco-
pies, performed both as primary screens and as follow-up to
positive noncolonoscopy tests.76 Finally, starting CRC
screening earlier also may contribute to reducing disparities
in population groups with a higher disease burden (includ-
ing blacks, Alaska Natives, and some American Indian
groups). Although the modeling analyses were unable to
include other racial groups or to distinguish Hispanic eth-
nicity, incidence rates for Asians and Hispanics are similar
to those for whites. Therefore, the general recommendation
to begin screening at age 45 years should be applicable to all
groups.
In summary, based on the recent increase in CRC inci-
dence in younger persons, the analyses demonstrating a
favorable benefit-to-burden balance for initiating screening
earlier, and the expected reduction in CRC mortality and
incidence, the ACS recommends that all adults start CRC
screening at age 45 years using any of the screening options
presented in Table 1.
Choice of Screening Tests
The recommendation for CRC screening includes offering
patients the opportunity to select either a structural (visual)
examination or a high-sensitivity stool-based test, depend-
ing on patient preference and test availability. As detailed in
Table 3, the screening options differ in the extent of patient
burden and in ways that can affect a patient’s choice of test
and subsequent adherence, including screening frequency,
screening location (home vs medical facility), need for die-
tary and/or bowel preparation, need for sedation, time and
transportation required, relative ability to prevent versus
detect CRC, out-of-pocket cost, risk of complications, and
test accuracy. There is evidence that patients will have a
preference for one type of screening test over others if pro-
vided sufficient information regarding these test attributes,
although no single test appears to consistently dominate
patient preferences, supporting a strategy of offering
choice.45,47,52,77,78 Intention to screen is also higher if the
screening test ordered is consonant with the patient’s prefer-
ence.47,77 Decision aids that help patients choose among
options have been shown to improve knowledge and interest
VOLUME 68 _ NUMBER 4 _ JULY/AUGUST 2018 261
262
TABLE 3. Considerations in Choosing a Colorectal Cancer Screening Testa
RECOMMENDED
SCREENING SCREENING EVIDENCE OF EFFECTIVENESS AND
TEST INTERVAL TEST PERFORMANCE
CA: A Cancer Journal for Clinicians
Stool-based screening tests
FIT with high Annual l Indirect evidence of mortality
sensitivity for cancer reduction from RCTs of guaiac-based
stool tests
l Equivalent or superior performance
compared with high-sensitivity
gFOBT
l Variability in test performance by
version and brand
gFOBT with high sensitivity Annual l Good RCT evidence for incidence
for cancer (HSgFOBT) and mortality reduction
l Performance characteristics vary by
version of the test (low-sensitivity
gFOBT versions are not
recommended for CRC screening)
mt-sDNA Every 3 y l Indirect evidence of mortality
(as per reduction from RCTs of guaiac-based
manufacturer) stool tests
l Results from one large,
manufacturer-funded trial showed
improved sensitivity for cancer and
advanced adenomas and poorer
specificity compared with FIT
LIMITATIONS
l High nonadherence to annual testing
(especially in absence of reminder
systems)
l Less effective for advanced adenoma
detection
l Few available tests have published
peer-reviewed performance data
l High nonadherence to annual testing
(especially in absence of reminder
system)
l Less effective for advanced adenoma
detection
l Difficulty in ascertaining test
performance among the many
FDA-cleared tests
l This is a new test, with limited data
on screening outcomes, and its
performance needs to be monitored
over time
l There may be uncertainty in
management of positive results
followed by a negative colonoscopy
PATIENT BURDEN
l Is done at home
l Many brands require only a single
sample
l No diet or medication restrictions
l Is done at home
l Requires multiple samples
l Requires dietary and medication
restriction
l Higher false-positive rate than FIT
leads to more colonoscopies
l Can be done at home
l Higher false-positive rate than FIT
COST AND REIMBURSEMENT
l Inexpensive compared with structural
examinations and mt-sDNA
ACS Colorectal Cancer Screening Guideline
l Follow-up colonoscopy for positive
test may be subject to out-of-pocket
costs
l Inexpensive compared with structural
examinations and mt-sDNA
l Follow-up colonoscopy for positive
test may be subject to out-of-pocket
costs
l More expensive than other
stool-based tests
l Follow-up colonoscopy for positive
test may be subject to out-of-pocket
costs
 TABLE 3. Continued
RECOMMENDED
SCREENING SCREENING EVIDENCE OF EFFECTIVENESS AND
TEST INTERVAL TEST PERFORMANCE LIMITATIONS PATIENT BURDEN COST AND REIMBURSEMENT

Structural (visual)
examinations for screening
Colonoscopy
Every 10 y l Non-RCT evidence of incidence and
mortality reduction
l Extrapolation from RCTs of
sigmoidoscopy demonstrating
mortality reduction
l Risk of bowel perforation/bleeding
and cardiopulmonary complications
of anesthesia
l Performance is dependent upon
adequacy of bowel preparation, the
cecal intubation rate, withdrawal
time, and adenoma detection rate
l Requires full bowel cleansing
l Requires time off work and a
chaperone (if sedation is used)
l Most expensive test, but currently
reimbursable for those with
insurance coverage
l Polypectomy and anesthesia may be
subject to out-of-pocket costs

l Offers both early detection and l Limited collection of quality data in

prevention of CRC through many settings
polypectomy
l Level of adherence to 10-y interval is
unknown
l Lower sensitivity for neoplasia in the
proximal than the distal colon
CTC Every 5 y l Extrapolation from RCTs of l Incidental extracolonic findings may l Requires full bowel cleansing l Relatively expensive and may not be
sigmoidoscopy demonstrating require workup, with unclear covered by insurance (not covered by
mortality reduction benefit-burden balance Medicare at this time)
l Sensitivity and specificity for cancer l Exposure to low-dose radiation l Colonoscopy required if test positive. l Follow-up colonoscopy for positive
and advanced adenomas comparable If same day colonoscopy is not pos- test may be subject to out-of-pocket
to colonoscopy sible, a second bowel cleansing will costs
be required before the follow-up
colonoscopy.
FS Every 5 y l Best evidence among structural l Does not examine the proximal l Pain and discomfort l Follow-up colonoscopy for positive
examinations for reducing mortality colon test may be subject to out-of-pocket
and incidence costs
l Concerns about lack of quality l Requires enema prior to procedure
standards, limited availability, failure
to achieve a complete examination
l Abnormal findings require second
endoscopic procedure (colonoscopy)

CRC, colorectal cancer; CTC, computed tomographic colonography; FDA, US Food and Drug Administration; FIT, fecal immunochemical test; FS, flexible sigmoidoscopy; gFOBT, guaiac-based fecal occult blood test; mt-
sDNA, multitarget stool DNA; RCT, randomized controlled trial. aThe American Cancer Society considers these options as acceptable choices for CRC screening in average-risk adults. Individuals should be given informa-

VOLUME 68 _ NUMBER 4 _ JULY/AUGUST 2018

tion on the characteristics related to prevention potential, effectiveness, accuracy, costs, and potential harms of available and accessible tests to make an informed decision on which test to choose for CRC screening.
All positive noncolonoscopy screening tests should be followed up with timely colonoscopy as a part of the screening process. Repeating positive noncolonoscopy tests is not acceptable.

263
CA CANCER J CLIN 2018;68:250–281
 ACS Colorectal Cancer Screening Guideline
in screening and lead to increased screening compared with
not providing information.79
Trials offering a choice between a stool test and a structural
examination compared with either test alone have generally
demonstrated greater uptake when a choice is offered. The
best evidence in the United States derives from a randomized
trial in a safety-net population comparing annual gFOBT ver-
sus colonoscopy versus choice between the 2 in which it was
demonstrated that choice was more effective than offering
colonoscopy alone. In the first year of the study, which
included patient navigation (year 1 only), the screening com-
pletion rate was 38% for patients offered colonoscopy, 66%
for those offered gFOBT, and 68% for those offered a
choice.80 While uptake overall was similar in the gFOBT
group versus the choice group, it is clear that a “colonoscopy-
only” referral resulted in substantially lower adherence.
Adherence to screening declined significantly in subsequent
years, reinforcing the importance of patient navigation,
reminder systems, and other support strategies in achieving
sustained adherence.80,81 A non-US prospective trial corrobo-
rated the finding that offering a choice of FIT or colonoscopy
led to significantly greater adherence than offering either test
alone.82 Although providing an array of screening options
may enhance uptake and allows patients to exert their auton-
omy, in one study, offering multiple test options was shown
to create confusion and decisional conflict, potentially leading
to poor adherence.83 There clearly is a need to provide clini-
cians with guidance and tools to facilitate decision making
that best meet patients’ needs and enhance uptake of
screening.
The GDG recognized that the complexity and time
requirements for implementing a choice among multiple tests
in the clinician-patient encounter may be burdensome. The
importance of offering a choice between structural or stool-
based testing is included in this guideline in recognition of
the role of patient values and preferences and as a practical
implementation strategy to improve adherence; clinicians
who experience time pressures that conflict with this impera-
tive should look to practice enhancements that take advan-
tage of team-based approaches among practice personnel.84,85
Importantly, the choice of screening test may be limited by
the local availability of high-quality test options or by patient
access to tests based on cost or other factors. In this instance,
there is little purpose in offering tests that are not readily
available and accessible. However, clinicians should be pre-
pared to describe/offer options that are available and intro-
duce additional options if the patient does not appear to be
accepting of the tests initially presented.
The information provided on characteristics of the tests
in this guideline is designed to facilitate clinician-patient
encounters and patient choices consistent with preferences
and thus, it is hoped, to increase utilization of CRC
264 CA: A Cancer Journal for Clinicians
screening. In addition, materials to facilitate decision mak-
ing in selecting a test at the point of care have been devel-
oped by the ACS to facilitate implementation of this
guideline and are available online (cancer.org/colonmd).86,87
Follow-up of positive noncolonoscopy screening tests
Implementation of the screening options included in this
guideline is premised on the requirement that the appropri-
ate follow-up to a positive (noncolonoscopic) test is a timely
colonoscopy. The follow-up colonoscopy should not be con-
sidered a “diagnostic” colonoscopy but, rather, an integral
part of the screening process, which is not complete until
the colonoscopy is performed. The information provided to
patients to facilitate a choice among tests must include the
importance of follow-up of a positive (noncolonoscopic) test
with colonoscopy. Repeating a positive stool-based test to
determine whether to proceed to colonoscopy is not an appropri-
ate screening strategy. A retrospective cohort study involving
70,124 patients with a positive FIT result examined the
relationship between time to colonoscopy after a positive
FIT result and risks of any CRC and of advanced-stage dis-
ease.88 There were no significant differences in the risk of
CRC with follow-up colonoscopy performed as late as 7 to
9 months after a positive FIT. After a delay of 10 months or
more, however, there was a 48% greater risk of CRC, and
the risk of stage III or IV disease was double that of those
who received colonoscopy in the first few months after a
positive FIT. The risks were even higher when colonoscopy
was delayed for 12 months or more (odds ratio, 2.25 for any
cancer and 3.22 for advanced-stage disease).88
The proportion of patients receiving timely colonoscopy
follow-up of positive stool blood test results is fair to poor in
many settings. Research has documented failure to complete
follow-up colonoscopy within 12 months of a positive stool
occult blood test in more than one-half of patients in some set-
tings.89,90 One study comparing completion rates among 4
health systems in the United States reported that rates of colo-
noscopy follow-up at 12 months varied from 58% to 83%. In
contrast, higher rates of timely colonoscopy follow-up have
been documented in organized screening programs. Program-
matic elements associated with higher completion rates
included explicit organizational targets for time to colonoscopy
after a positive stool blood test and performance monitoring
with monthly reporting.91 A recent systematic review endorses
the impact of giving providers performance data and reminders
and also suggests that patient navigation may increase the rate
of colonoscopy completion in this circumstance.92
When to Stop CRC Screening
 The ACS recommends that average-risk adults in
good health who have a life expectancy of greater
than 10 years continue colorectal cancer screening
through the age of 75 years (qualified recommendation).

 The ACS recommends that clinicians individualize
screening decisions for individuals aged 76 through
85 years, based on patient preferences, life expec-
tancy, health status, and prior screening history
(qualified recommendation).
 The ACS recommends that clinicians discourage
individuals over age 85 years from continuing screen-
ing (qualified recommendation).
There is evidence from RCTs to support CRC screening up
to age 75 years in average-risk populations. The US-based
Prostate, Lung, Colon, and Ovarian Cancer Screening
(PLCO) trial of FS enrolled patients aged 50 to 74 years, and
all but one of the gFOBT trials that met acceptable quality
standards enrolled patients to at least age 75 years. The US-
based gFOBT trial enrolled patients through age 80 years.26,29
Each of these trials demonstrated reductions in CRC mortal-
ity, thus providing an empiric basis for recommending screen-
ing average-risk individuals in good health up to age 75 years.
Beyond age 75 years, there is greater uncertainty about
the benefit-harm tradeoff for CRC screening. On the basis
of data from gFOBT randomized trials, the lag time to
CRC screening benefit has been estimated to be 10 years,93
although this benefit represents a combination of early
detection (the benefit is realized sooner than 10 years) and
prevention (the benefit is realized after 10 years). Thus, a
screening benefit is generally believed to require a minimum
10-year life expectancy. Modeling results indicate that there
is little incremental benefit in terms of LYGs for continuing
screening after age 75 years in individuals who have been
screened regularly from the earliest recommended starting
age.30 However, this often will not be the case, and the
absence of a history of normal examinations will be of
greater concern for those adults who have not been adherent
to recommended screening in the years just before age 75
years. Although the current modeling analyses did not strat-
ify by comorbidity status, previous studies have demon-
strated that screening outcomes will be heavily influenced
by comorbidity and functional status.94-96 Moreover, CRC
incidence and mortality continue to rise after age 75 years,
thus indicating an ongoing opportunity to decrease CRC
morbidity and mortality by screening individuals in this age
group who are in good health (ie, are expected to live long
enough to benefit and are at low risk for treatment compli-
cations). The impact of colonoscopy on preventing CRC in
the elderly was recently examined in a prospective observa-
tional cohort study of Medicare beneficiaries aged 70 to 79
years who had no diagnostic or surveillance colonoscopies in
the past 5 years.97 Among adults aged 70 to 74 years, the
absolute risk of CRC over 8 years was reduced by 16% in the
group undergoing colonoscopy versus the no-colonoscopy
group (2.19% vs 2.62%, respectively), while risk reduction
was notably less in individuals aged 75 to 79 years who
CA CANCER J CLIN 2018;68:250–281
underwent colonoscopy versus the no-colonoscopy group
(2.84% vs 2.97%, respectively).
The harms of screening and diagnostic colonoscopy,
including bleeding, perforation, complications of anesthesia,
and hospitalization, are greater in the elderly, particularly
those older than 80 years, and the risk increases with
increasing comorbidity burden.97,98 In the Medicare cohort
study mentioned above, the risk of adverse events from colo-
noscopy was nearly twice as high among individuals aged 75
to 79 years (10.3 per 1000) compared with individuals aged
70 to 74 years (5.6 per 1000).97
Given increased competing mortality risks and the
increased risk of colonoscopy-associated complications with
greater age, the focus of screening among individuals aged
76 to 85 years should be on healthy individuals with no or
few comorbidities who are expected to live at least 10 years.
The yield would be expected to be higher in those not up to
date with screening.95 If there is concern regarding colonos-
copy risks, then noncolonoscopy options may be preferable.
Given the paucity of evidence to inform screening decisions
in this age group, patient preference should weigh heavily in
the decision. A recent examination of older individuals’
views suggested that patients may be receptive to a discus-
sion with a clinician of screening cessation based on age and
health status, but not emphasizing limited life expectancy.99
There are tools that are useful for estimating life expectancy
considering an individual’s comorbidity and functional
status.100,101
After age 85 years, the competing mortality risks and
risks of CRC screening complications are sufficiently high
that it is reasonable to conclude that the potential harms of
screening outweigh the potential benefits in this age group.
Consequently, health care professionals should not offer
screening to individuals in this age group. There may be
exceptional circumstances when screening might be consid-
ered, such as the individual in excellent health who has not
been engaged in routine screening and strongly desires test-
ing; but, in general, screening should be discouraged in indi-
viduals older than 85 years.
Options for CRC Screening
Stool-Based CRC Screening Tests
There is consistent RCT evidence to support the use of
stool testing for CRC screening. The first tests shown to be
effective in screening for CRC were guaiac-based tests
(gFOBT), which detect peroxidase activity involving the
heme portion of the hemoglobin molecule. Consequently,
both low-sensitivity and high-sensitivity gFOBT are vul-
nerable to false-positive results from nonsteroidal anti-
inflammatory drugs that can cause upper gastrointestinal
(GI) bleeding, red meat, and dietary peroxidases (found in
some vegetables and fruits) as well as false-negative results
VOLUME 68 _ NUMBER 4 _ JULY/AUGUST 2018 265
 ACS Colorectal Cancer Screening Guideline
from antioxidants, such as vitamin C.102 In contrast, immu-
nochemical tests (FITs) use antibodies that selectively detect
the globin component of human hemoglobin, which pro-
vides advantages over gFOBT. Because globin is degraded
by digestive enzymes found in the upper GI tract, the posi-
tivity of FIT is generally not influenced by upper GI bleed-
ing.102 Furthermore, because the antibody is specific to
human hemoglobin, FITs are not vulnerable to interference
from medications, animal hemoglobin (red meat), or peroxi-
dases from foods, thus eliminating the need for the dietary
restrictions that are recommended with gFOBT. A third
stool test is the mt-sDNA test, which combines an immu-
nochemical assay for hemoglobin, and assays for aberrantly
methylated BMP3, NDRG, and NDRG4, mutated K-ras,
and b-Actin in cells exfoliated from colonic neoplasms.103
Currently, there is only one mt-sDNA test marketed in the
United States.104 (See the online Supporting Information
for a more detailed discussion of each test.)
All manufacturers of stool tests recommend that stool col-
lected for CRC screening should be collected at home.
However, because gFOBT and FIT require the collection of
only small samples of stool, some clinicians bypass the rec-
ommendation for home testing by using a single sample of
stool collected during digital rectal examination. It has been
demonstrated that this practice fails to detect up to 90% of
cancers.105,106 Because of this very low sensitivity for CRC
and lack of validation studies, CRC screening guidelines rec-
ommend against in-office testing with stool collected during
digital rectal examination. Some practices have implemented
screening programs that give patients the option of testing a
spontaneously passed bowel movement in a dedicated clinic
bathroom.
Performance characteristics of individual gFOBT and
FIT versions vary. The US Food and Drug Administration
(FDA) clearance process does not require manufacturers to
provide information on the sensitivity or specificity of their
test for the detection of CRC or adenomatous polyps, and
tests specifically are cleared only for the detection of occult
blood, not for CRC screening. This approach to clearance
poses a challenge to clinicians seeking to choose a stool test
with high accuracy. The poor performance of nonrehy-
drated, low-sensitivity gFOBT means that these gFOBT
variants cannot be recommended and should not be used for
CRC screening, although they still are available in the mar-
ketplace. At the time of publication, the only guaiac test
evaluated in a population-based study shown to meet per-
formance standards to qualify as a high-sensitivity test
(HSgFOBT) is Hemoccult II Sensa (Beckman Coulter
Inc., Brea, CA), although there may be other variants that
have high sensitivity. The sensitivity of HSgFOBT ranges
from 62% to 79%, with specificity ranging from 87% to
96%.26,107,108
266 CA: A Cancer Journal for Clinicians
FITs consistently demonstrate superior sensitivity for
cancer and advanced neoplasia and slightly lower specificity
compared with low-sensitivity gFOBT. Compared with
HSgFOBT, the sensitivity and specificity of FIT tend to be
similar or superior. Sensitivity for single-sample FIT ranges
from 73% to 92%, and specificity ranges from 91% to
97%.102,109-112 However, most brands of FIT have limited
evidence demonstrating their accuracy for detection of
CRC. Daly et al found published data from colonoscopy-
confirmed studies of FIT performance for only 6 of the 26
versions of FIT sold in the United States.113 Because studies
have shown variable performance of different FITs across
studies in which individuals undergo multiple tests to com-
pare outcomes,114-116 it should not be assumed that versions
of FIT that lack published data have suitable performance
characteristics.117
The original, low-sensitivity guaiac tests have largely
been superseded by HSgFOBT and FIT in organized
screening programs around the world, and a similar shift is
underway in the United States.102,118-120 National surveys
of CRC screening test utilization do not distinguish
between FIT and gFOBT, but overall use of stool testing in
the United States is low. In 2015, 7.2% of US adults aged
50 years and older reported having completed a take-home
stool-based test (FIT or gFOBT) within the past year.65
The effectiveness of annual testing depends upon program
sensitivity, which depends on multiple, annual opportunities
for detection before a cancer or an advanced lesion becomes
symptomatic.121
In the 2018 MISCAN modeling analysis for the general
population under the increased-risk scenario, in which all
stool tests were grouped in the same class, annual FIT from
ages 45 to 75 years yielded 94% of the LYGs compared
with the benchmark strategy (colonoscopy every 10 years
from ages 45 to 75 years) and was found to be a model-
recommendable strategy.34 In contrast, annual HSgFOBT
from ages 45 to 75 years was not among the model-
recommendable strategies (Table 2).34 Although annual
HSgFOBT and FIT from ages 45 to 75 years achieved the
same LYGs (403 LYGs), HSgFOBT was less efficient; for
a given number of colonoscopies, more LYGs were achiev-
able with FIT compared with HSgFOBT, because the
higher false-positive rate of HSgFOBT led to more
colonoscopies.
There are no direct harms of CRC screening associated
with HSgFOBT and FIT. Harms are associated with injury
to the colon or other complications related to colonoscopy
performed after a positive HSgFOBT29 (see Colonoscopy
section, below).
In the guideline update, HSgFOBT (eg, Hemoccult II
Sensa) remains an option for CRC screening, because it has
high sensitivity approaching that of FIT and because of its

lower costs compared with FIT, making it an attractive option
in low-resource settings where FIT may not be affordable.
The best evidence for the performance of mt-sDNA test-
ing comes from a large, manufacturer-funded, multicenter,
comparative trial of mt-sDNA and FIT testing in average-
risk individuals using colonoscopy as the reference stan-
dard.103 The sensitivity of mt-sDNA for CRC was 92.3%,
compared with 73.8% for FIT. When the specificity of FIT
was matched to that of mt-sDNA (86.6%), its sensitivity to
detect CRC improved to 77% but remained significantly
below that of mt-sDNA. The sensitivity for advanced ade-
nomas and sessile serrated polyps also was higher for
mt-sDNA compared with FIT (42.4% vs 23.8%). One sig-
nificant advantage of mt-sDNA compared with FIT was its
higher detection rate of serrated sessile polyps >1 cm (sensi-
tivity was 42.4% for mt-sDNA and 5.1% for FIT).
The specificity of mt-sDNA was significantly lower than
that for FIT: 89.8% versus 96.4%, respectively, for partici-
pants with a negative colonoscopy, indicating a higher false-
positive rate with mt-sDNA.
Like other stool-based tests, the harms of mt-sDNA are
associated with the harms of colonoscopy performed for the
follow-up of positive tests (see Colonoscopy section below).
However, an issue unique to mt-sDNA compared with FIT
and HSgFOBT is the uncertainty about the interpretation
of a negative follow-up colonoscopy after a positive finding
on mt-sDNA. Reported results from the mt-sDNA test cur-
rently available in the United States do not indicate which
component of the test (FIT or DNA) yielded the positive
result. A positive stool DNA test followed by a negative
colonoscopy may be caused by failure to detect a visible
lesion, neoplastic changes that are not yet visible, or the pres-
ence of noncolonic aerodigestive or supracolonic neoplasms.
Patients with positive mt-sDNA results and a negative
follow-up colonoscopy may undergo more aggressive short-
term surveillance because of heightened concerns related to
unresolved false-positive findings. In 2 follow-up studies of
patients with false-positive results on mt-sDNA with
median follow-up of approximately 4 years, no excess rates
of CRC or aero-digestive malignancies were identi-
fied.122,123 In a more recent study by Cooper et al that
included follow-up mt-sDNA, colonoscopy and upper
endoscopy among 12 patients who had prior positive mt-
sDNA results and a negative colonoscopy, 7 patients had
negative stool tests and colonoscopies, whereas 3 among the
remaining 5 patients had positive findings on their follow-up
colonoscopy (2 advanced and 1 nonadvanced adenoma).124
Longer term follow-up will be required to provide greater
reassurance and guide management, but the findings from
Cooper et al are a reminder that high-quality colonoscopy is
critically important, especially in the proximal colon, when
following up positive findings on an mt-sDNA test.
CA CANCER J CLIN 2018;68:250–281
In the general population modeling analysis conducted
for this guideline update, mt-sDNA was not shown to be a
model-recommendable test. Annual mt-sDNA was found
to be inefficient within the class of stool tests because of
the higher number of colonoscopies required per LYG
(Table 2).34 Mt-sDNA every 3 years (the screening fre-
quency on which FDA clearance was based) yielded 88% of
the LYGs from colonoscopy every 10 years (less than the a
priori criterion of 90%) and 93% of the LYGs compared
with annual FIT testing (Fig. 5).34
The GDG concluded that mt-sDNA warrants inclusion
among test options based on its sensitivity for detecting
CRC, its improved advanced adenoma and serrated sessile
polyp detection compared with FIT, and evidence indicat-
ing that some adults would choose screening with mt-
sDNA over other CRC screening tests.125
Options for CRC Structural (Visual) Examinations
Structural (visual) examinations used for CRC screening are
procedures that allow the examiner a visual inspection of the
bowel. These include endoscopic examinations (FS and
colonoscopy) and a radiologic examination (CTC). One
feature that distinguishes structural examinations from stool
testing is the longer recommended screening interval (see
Supporting Information for a more detailed discussion of each
test).
Structural examinations place more demands on patients
than stool testing. All structural examinations require bowel
cleansing before the examination: for FS, bowel cleansing
rectal enemas are recommended and, for colonoscopy and
CTC, the most common bowel cleansing preparation
involves ingestion of polyethylene glycol oral laxatives, and
patients are usually advised to replace solid foods with a liq-
uid diet the day before bowel cleansing. In a recent system-
atic review of the effectiveness of various bowel cleansing
protocols, the USMSTF noted that the length of time
between the last dose of preparation and the initiation of
colonoscopy is correlated with the quality of cleansing in the
proximal colon. When bowel cleansing is split between the
day before and the day of colonoscopy, the data consistently
demonstrate superior bowel cleansing performance.126 On
the basis of these findings, the USMSTF strongly recom-
mends use of a split-dose bowel cleansing regimen for elec-
tive colonoscopy (strong recommendation, high-quality
evidence) and, alternatively, a same-day regimen for patients
undergoing an afternoon examination (strong recommenda-
tion, high-quality evidence).126 Colonoscopy usually is per-
formed with sedation, thus requiring a day away from work
and a chaperone to provide transportation. FS and CTC
usually are performed without sedation, entailing less time
commitment than colonoscopy.
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 ACS Colorectal Cancer Screening Guideline
The adequacy of bowel preparation and expertise of clini-
cians performing structural examinations are critical to the
effectiveness of CRC screening with structural examina-
tions. Primary care clinicians should ascertain the degree to
which recommended quality-assurance programs127-131 are
in place and, in particular, whether the practice is monitor-
ing performance metrics, including the adenoma detection
rate.
Colonoscopy
Colonoscopy is the most frequently used CRC screening
modality in the United States.65 It allows direct visual
inspection of the entire colon and same-session detection,
biopsy, and removal of polyps. Colonoscopy also is used for
further evaluation of patients who have had a positive test
result on a noncolonoscopy CRC screening examination.
The best direct evidence of effectiveness comes from a large,
prospective, observational cohort study132 in which the
authors reported a hazard ratio (HR) for CRC mortality of
0.32 (95% confidence interval [95% CI], 0.24-0.45) com-
paring 1 or more colonoscopy versus no colonoscopy over
24 years, with better results for distal cancers (HR, 0.18;
95% CI, 0.10-0.31) than for proximal cancers (HR, 0.47;
95% CI, 0.29-0.76). Incidence reduction was demonstrated
for individuals who had a negative colonoscopy, with an
HR of 0.53 (95% CI, 0.40-0.71).132 In the systematic evi-
dence review, colonoscopy sensitivity for detecting adeno-
mas 6 mm (using CTC as the comparator) ranged from
75% to 93%, with a specificity of 94%, and sensitivity for
adenomas 1 cm ranged from 89% to 98%, with a specific-
ity of 89%.29
The 3 CISNET models that informed the USPSTF’s
2016 CRC screening recommendation statement44 esti-
mated that colonoscopy screening every 10 years from ages
50 through 75 years would reduce CRC incidence by 62%
to 88% and mortality by 79% to 90%, averting 22 to 24
deaths from CRC per 1000 individuals screened. The
median LYGs (270) was superior to that of other testing
options.30 In the general-population MISCAN modeling
conducted for the ACS using updated incidence data, colo-
noscopy every 10 years from ages 45 through 75 years pro-
vides a greater reduction in the lifetime risk of CRC and
somewhat more LYGs and CRC deaths averted than other
recommendable strategies (Fig. 5),34 although it requires
more than twice the number of lifetime colonoscopies as
stool-based testing (Table 2).34
There is a risk of overdetection and removal of small pol-
yps that have low likelihood of progressing to cancer,
increasing the risks associated with polypectomy and poten-
tially leading to unnecessary recommendations for short-
term surveillance. Colonoscopy is significantly more likely
to miss sessile serrated polyps than typical adenomas.133,134
268 CA: A Cancer Journal for Clinicians
The primary harms from screening colonoscopy include
perforation and bleeding, which occur more commonly if
polypectomy is performed. The USPSTF evidence synthesis
estimated that the risk of perforation is approximately 4 per
10,000 colonoscopies, and the risk of major bleeding is
approximately 8 events per 10,000 colonoscopies.29 The
complication rate of colonoscopies performed to follow up
positive noncolonoscopy screening tests is significantly
higher than that for primary screening colonoscopies.26,40
Importantly, the harms of colonoscopy rise significantly and
nonlinearly with age and comorbidity burden.135 In a
population-based study of 1.6 million Californians undergo-
ing colonoscopy that was published after the USPSTF evi-
dence review, the rate of lower GI bleeding was 5 per
10,000 among those not undergoing biopsy and 36 per
10,000 among those undergoing biopsy or other interven-
tion. The comparable perforation rates were 3 per 10,000
and 6 per 10,000, respectively. Thirty-day non-GI compli-
cations were reassuringly low in that study; the risk of myo-
cardial infarction was 2.5 per 10,000 for colonoscopy
without biopsy and 4 of 10,000 with biopsy, which was
lower than that for comparator procedures (joint aspiration/
injection and lithotripsy).41
Computed tomography colonography
CTC, sometimes referred to as “virtual colonoscopy,”
involves the acquisition of thin-slice computed tomography
images that can be evaluated as 2-dimensional images or
reconstructed into 3-dimensional images of the colorectal
lumen, creating views previously available only through a
colonoscope. In the 2 largest and highest quality studies of
CTC, CRC detection rates with CTC were essentially
identical to those achieved with optical colonoscopy.136,137
A systematic review and meta-analysis of 49 studies using
colonoscopy as the reference standard estimated that the
sensitivity of CTC for cancer detection was 96.1%, and the
sensitivity for adenomas >6 mm ranged from 73% to 98%
with a specificity of 89% to 91%.138
Screening every 5 years with CTC from aged 50 through
75 years was considered a model-recommendable strategy in
the 2016 analyses conducted for the USPSTF.30,31 The
general-population modeling analysis commissioned for the
ACS, using updated incidence data, also found that CTC
every 5 years from ages 45 through 75 years was a model-
recommendable strategy (Table 2).34
Adverse events associated with CTC include those associ-
ated with bowel preparation, such as abdominal pain, exami-
nation related pain, and vasovagal syncope or presyncope.
Potentially more serious harms, although very rare, include
perforation and the possibility of an induced cancer associ-
ated with radiation exposure from single or multiple exami-
nations. A more common occurrence, which may or may not
be beneficial, is the identification of extracolonic findings.

Perforation, mostly due to insufflation, is very rare and is
estimated to occur in less than 2 per 10,000 procedures.29 As
with any imaging test, radiation exposure commonly is
raised as a potential harm, although new screening protocols
have resulted in substantial dose reductions, with average
doses ranging from <1 to 2 millisieverts (mSv) in recent
reports,139,140 which is less than the 3-mSv-per-year esti-
mate of average background radiation exposure in the
United States.141 This low level of exposure every 5 years
has been judged to be a negligible harm when considered in
the context of the potential LYGs from avoiding a prema-
ture CRC death.142
The detection of incidental extracolonic findings with
CTC screening is an area of concern. The USPSTF evi-
dence report concluded that, based on empiric evidence, it
remains unclear whether extracolonic findings represent a
net benefit or harm.26 In their review of 21 studies ranging
in size from 75 to 10,286 patients, Lin et al observed that
E4 findings, which are potentially important findings that
are judged to require further follow-up, ranged from 1.7%
to 12%.26
Patients with polyps of significant size will require
follow-up colonoscopy to remove the polyps. While same-
day colonoscopy for polyp removal can be offered without
the need for additional preparation, this requires coordina-
tion between medical specialists (radiologists and endoscop-
ists) and facilities (radiology departments and endoscopy
suites).143 If this coordination is not in place, patients who
have abnormalities detected at CTC must be scheduled for
follow-up colonoscopy in the future, necessitating a repeat
of the cathartic bowel preparation and additional time
commitment.
Flexible sigmoidoscopy
FS, the first visual inspection examination demonstrated to
be effective for CRC screening,144,145 is an endoscopic pro-
cedure that examines the lower half of the colorectal lumen.
It is typically performed without sedation and with a more
limited bowel preparation than the other structural exami-
nations, usually 1 or 2 enemas. CRC incidence and mortal-
ity reductions have been demonstrated by 4 RCTs of FS
with 1 or 2 screening examinations (at intervals of every 3-5
years).145-148 In the pooled analysis conducted for the
USPSTF,26,29 CRC mortality was reduced by 27% over 11
or 12 years of follow-up (relative risk, 0.73; 95% CI, 0.66-
0.82). Mortality reduction was significant for distal CRC,
but not proximal CRC. CRC incidence was reduced by
21%. PLCO investigators reported significant reductions in
the incidence of both distal and proximal cancers.29 A recent
17-year follow-up of the UK Flexible Sigmoidoscopy
Screening Trial reported a 26% reduction in the incidence
of CRC and a 30% reduction in mortality. As in the pooled
analysis, the overall effectiveness of screening in the UK trial
CA CANCER J CLIN 2018;68:250–281
derived from the detection of distal lesions, as there was no
significant reduction in incidence or mortality for proximal
cancers.149 A recent pooled analysis of 3 of the 4 trials
(PLCO, SCORE, and Norwegian Colorectal Cancer Pre-
vention [NORCCAP]) with a median of 10 to 12 years of
follow-up reported an overall 21% reduction in CRC inci-
dence and a 27% reduction in mortality with screening
FS.150 However, neither incidence nor mortality was low-
ered by FS in women aged 60 years or older, primarily
because of the poorer performance of FS in detecting proxi-
mal colon cancers, which disproportionately affected older
women.
In the MISCAN modeling analyses adjusted for
increased incidence, FS every 5 years from ages 45 through
75 years was a model-recommended strategy. In contrast,
assuming stable incidence, in the CISNET analysis con-
ducted for the USPSTF 2016 update, FS alone every 5 years
or 10 years in adults aged 50 to 75 years was not a model-
recommended strategy.30 The greater efficiency of FS in the
updated model is likely attributable to the observation that
most of the increased incidence is confined to the rectum
and distal colon (Fig. 5).34
The use of FS as a CRC screening test has declined
markedly over the past several decades in the United States,
having been replaced by colonoscopy as the primary struc-
tural examination. As of 2010, only 2.5% of adults aged 50
to 75 years reported having an FS in the recommended
interval, compared with 60% for colonoscopy.151
Despite evidence for the efficacy of FS as a CRC screen-
ing test in expert settings, the low level of utilization of FS
in the United States raises questions as to whether
community-based clinicians have received adequate training
or perform a sufficient number of procedures to maintain
proficiency. Standards, including depth of insertion, ade-
noma detection rate, and adequacy of preparation, have
been proposed,130 but rigorous quality standards are not
currently in place in the United States. Despite the robust
body of RCT evidence demonstrating the effectiveness of
FS, low utilization rates coupled with quality concerns led
the GDG to consider removing FS as a recommended test.
The decision was made to retain it based primarily on the
foundation of evidence it provides of a mortality reduction
benefit from screening with structural examinations. In
addition, there was an acknowledgment that FS might be
the primary structural examination available in some geo-
graphic areas.
Emerging Technologies Not Currently
Recommended for Routine Screening
The following tests are not among the list of recommended
CRC screening options but have been cleared by the FDA
for use in special circumstances.
VOLUME 68 _ NUMBER 4 _ JULY/AUGUST 2018 269
 ACS Colorectal Cancer Screening Guideline
Methylated Sept9 DNA
The FDA recently cleared a blood test to detect circulating
methylated Septin 9 DNA (mSEPT9), a molecular CRC
biomarker shed by the tumor into the circulation, as a test
for average-risk individuals who have repeatedly refused
other forms of CRC screening.152 According to the FDA,
all tests that are available and recommended in the USPSTF
CRC screening guidelines should be offered and declined
before offering the mSept9 test. Because patients with a
positive mSept9 test should be referred for colonoscopy,
they must be prepared to undergo a follow-up test that they
previously had rejected for screening.
Most studies of mSept9 have been tandem studies com-
paring advanced neoplasia detection rates with a conven-
tional CRC screening test. The USPSTF evidence report
included one prospective study of mSept9 that showed a
sensitivity and specificity of 48% and 91%, respectively, for
detecting CRC in an average-risk population scheduled to
undergo colonoscopy.29,153 Since the USPSTF review, a
retesting of samples from the same prospective cohort using
a newer version of the test yielded an improved sensitivity
for cancer and advanced adenomas of 68% but a lower spe-
cificity of 80%.154 A second study using the newer version
of the test involving US subjects undergoing screening colo-
noscopy reported similar sensitivity and specificity for
screen-detected CRC (73% and 82%, respectively).155
Although these studies demonstrate improving test sensi-
tivity, concerns remain about poor specificity compared with
recommended screening options and the limited base of evi-
dence in asymptomatic, screening populations. In addition,
there has been no microsimulation modeling of the newer
version of the test to estimate its benefit, a benefit-harm ratio,
or a screening interval for regular testing, which also has not
been established by the manufacturer. In addition, mSept9 is
a novel blood test for CRC early detection with no compara-
ble screening tests from which to infer a benefit in terms of
critical outcomes (CRC mortality or incidence reduction), as
there are for the included screening test options. Importantly,
the test has not been cleared by the FDA for unrestricted use
in general routine screening. Going forward, the performance
of plasma DNA tests should be monitored. An accurate
blood test would have obvious value in the repertoire of
screening options, and even a test with somewhat poorer per-
formance would likely make a contribution in adults persis-
tently nonadherent to screening recommendations. In both
instances, adherence would likely be high. However, based
on the limitations noted above, at this time, mSept9 is not
included in this guideline as an option for routine CRC
screening for average-risk adults.
Capsule endoscopy
Early versions of capsule endoscopy, also known as capsule
colonoscopy, principally were used to evaluate the small
270 CA: A Cancer Journal for Clinicians
bowel, but interest has grown in the past decade to apply
this technology to CRC screening. The device incorporates
a camera on both sides of an ingestible capsule that captures
images of the colon and rectum as it passes through the GI
tract. The images are recorded and stored in an external
device worn by the patient and later analyzed by a clinician.
The test is complete when the capsule is passed in the
stool.156
In a systematic review157 of the diagnostic accuracy and
safety of colon capsule endoscopy for the detection of colo-
rectal polyps in persons with signs or symptoms of CRC or
at high risk for the disease, the reported pooled sensitivity
and specificity of capsule endoscopy were 87% (95% CI,
77%-93%) and 76% (95% CI, 60%-87%), respectively, for
the detection of a colorectal polyps 6 mm. The results
showed improved test performance for larger polyps (at least
10 mm), with pooled sensitivity of 89% (95% CI, 77%-
95%) and specificity at 91% (95% CI, 86%-95%).157
Adverse events associated with capsule endoscopy were
reported in <4% of patients, which mostly included nausea,
vomiting, abdominal pain, and fatigue from the required
bowel preparation.157 Capsule retention is the most serious
reported problem and occurred in 0.8% of patients (95% CI,
0.2%-2.4%). Like other endoscopic procedures, capsule
endoscopy requires adequate cleansing of the colon and, if
polyps are found, a colonoscopy may be needed to further
investigate and remove precancerous polyps.
In 2014, the FDA cleared the capsule endoscopy system
“for use only in patients who had an incomplete optical
colonoscopy with adequate preparation, and a complete
evaluation of the colon was not technically possible”158 and,
in 2016, capsule endoscopy was cleared for identifying the
location of colon polyps in patients suffering from lower GI
bleeding.159 Capsule endoscopy does not have FDA clear-
ance for CRC screening.
Decision Making and Clinical Considerations
Clinician roles in decision making
This update of the ACS CRC guideline emphasizes the
importance of patient preferences and choice to improve
uptake and adherence to CRC screening (see Choice of
Screening Test, above). Health care professionals and the
systems in which they work have a vital role in implement-
ing the ACS recommendation that adults undergo regular
screening with either a structural (visual) examination or a
high-sensitivity stool-based test, depending on patient pref-
erence and test availability. In most settings, either an FIT
or an HSgFOBT will be available through the practice and,
depending on the patient’s insurance coverage, mt-sDNA
may be an option. Colonoscopy is the most commonly avail-
able structural examination. In a growing number of set-
tings, CTC will be available and, for non-Medicare

beneficiaries, may be covered by the patient’s insurance.
In some settings, FS may be the most readily available
structural examination. From a practical implementation
standpoint, the choice offered will usually be among 1 or 2
stool-based tests and 1 or 2 structural examinations. The
offering of a choice applies primarily to the uptake of screen-
ing by individuals who are initiating screening or have failed
to adhere to prior recommendations for screening; for these
patients, exploring test preferences may be particularly effec-
tive to improve adherence to screening. For individuals who
have been adherent to screening, it is reasonable for clini-
cians to continue ordering the same previously completed
test without offering new options, unless the patient raises
specific concerns. The ACS recognizes that, in some set-
tings (eg, rural or low-resource settings), there may be only
one high-quality screening option available for many
patients, in which case, discussing a menu of unavailable
options is not useful.
Resources for clinicians and patients
This guideline provides a list of options for CRC screening
along with considerations for decision making to assist
health professionals and patients in selecting the option
most likely to be completed (Table 3). In addition, a
clinicians’ guide and decision support materials have been
developed to accompany this guideline to facilitate the
decision-making process.86 It is anticipated that these mate-
rials will help both uptake of and adherence to CRC screen-
ing by better aligning the selected screening test with
patient preferences. The materials can be found online at
cancer.org/colonmd.87
Patient considerations of cost and reimbursement
There are several important issues for clinicians and patients
to keep in mind with regard to the costs of CRC screening.
There is wide variation in the costs of screening, depending
on which test is chosen, with guaiac and fecal immuno-
chemical tests at the low end ($20-$30),160 colonoscopy
usually priced between $1000 and several thousand dol-
lars,161 and other testing methods falling between these 2
extremes. Patient out-of-pocket costs for each of these tests
may also vary, depending on a variety of factors, including
insurance status (insured vs uninsured), type of insurance
(ie, low-deductible vs high-deductible plans), and site of
service (eg, hospital vs free-standing endoscopy center and
within-network vs out-of-network). Insurance policy and
interpretation of coding rules may also impact patient costs
for CRC screening.
A stipulation in the Patient Protection and Affordable
Care Act (ACA) requires provision of preventive services
that receive an “A” or “B” recommendation from the
USPSTF, including CRC screening, with no copay or
deductible for beneficiaries. This provision applies to
CA CANCER J CLIN 2018;68:250–281
Medicare and to most commercial insurance plans, and
there is evidence that the ACA’s elimination of cost-sharing
contributed to increases in CRC screening among low-
income Medicare beneficiaries.162 This waiver of cost-
sharing is required only for screening examinations. Many
patients choosing colonoscopy as their initial screening test
will have the procedure with no out-of-pocket costs, but
patients covered by Medicare currently incur costs if a polyp
is removed, and patients with commercial insurance may
still be charged inappropriately for polyp removal during an
examination initiated for screening (see below). Further-
more, ACA provisions have been interpreted differently by
some insurers; some insurers have judged a personal history
of cancer, polyps, or a family history as defining all subse-
quent colonoscopies as diagnostic, especially if they are per-
formed at shorter intervals than were recommended by the
USPSTF for average-risk adults, thus resulting in charges
to the patient. Furthermore, if a patient is first screened
with a stool test or any other noncolonoscopy examination,
then most insurers interpret a colonoscopy performed to
follow up a positive initial screen as a diagnostic procedure,
meaning that the patient becomes responsible for cost-
sharing.163 A small number of insurers, recognizing that
this policy encourages some patients to choose colonos-
copy to avoid possible out-of-pocket costs, have opted to
treat the colonoscopy after a positive stool test as a contin-
uation of the screening process; legislation in Oregon
requires insurers that sell products in that state to treat the
follow-up colonoscopy in this manner.164 Patients living
in states that do not have this provision should be
informed that, if they choose a noncolonoscopy option as
their initial screening test and have an abnormal result,
then they may be responsible for some of the costs of colo-
noscopy. This ACS guideline update strongly recom-
mends that follow-up colonoscopy should be regarded as a
part of the continuum of the screening process rather than
a diagnostic procedure.
A second policy issue that may impact patient cost also
relates to the operational definition of a screening colonos-
copy. During implementation of the ACA, many insurers
used a narrow classification of screening colonoscopy to
guide application of the “no cost-sharing” provision. If a
lesion was biopsied or removed during a procedure that had
originally been scheduled as a screening colonoscopy, the
procedure would often be recoded as a diagnostic examina-
tion and thus belatedly and unexpectedly become subject to
patient cost-sharing. In 2013 the US Departments of Labor,
Health and Human Services, and the Treasury clarified that
this was not the intent of the ACA provision on preventive
services, issuing guidance to insurers stating that, “polyp
removal is an integral part of a colonoscopy” and indicating
that commercial plans “may not impose cost-sharing with
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 ACS Colorectal Cancer Screening Guideline
respect to a polyp removal during a colonoscopy performed
as a screening procedure.”165 Subsequent communications
to insurers clarified that anesthesia and pathology services
and bowel preparation medications provided in conjunction
with a screening colonoscopy must also be covered without
cost-sharing.166-168 Unfortunately, these rule clarifications
do not currently apply to the Medicare program; Medicare
beneficiaries frequently experience unexpected out-of-
pocket liabilities for “screening” colonoscopy if tissue is sam-
pled during the procedure. A recent modeling analysis
showed that waiving copays would have a favorable impact
on health improvements and costs.169 Changing the imple-
mentation of this element of the ACA in the Medicare pro-
gram will require federal legislative action.
Insurance coverage policies related to CRC screening are
largely driven by the linkage of the ACA’s preventive serv-
ices provisions to USPSTF recommendations. The current
USPSTF recommendation to begin CRC screening at age
50 years sets a minimal threshold for insurers; there is no
prohibition against coverage for screening at an earlier age.
However, it is likely that, in the near term, many individuals
aged 45 to 49 years will experience challenges with insur-
ance coverage for their screening examinations and may
experience out-of-pocket costs if they seek to begin screen-
ing. The ACS and other organizations are working aggres-
sively to educate insurers and policymakers on the rising
rates of CRC among younger individuals, the evidence in
support of screening for individuals aged 45 to 49 years, and
the importance of expanding screening coverage to this
group.
Interventions to increase utilization and adherence
Poor utilization of and adherence to CRC screening is a
major contributor to avoidable CRC mortality in the United
States and has been a persistent challenge since the earliest
prospective studies of CRC screening were conducted. A
systematic review of 100 prospective studies of participation
after first-time invitation found that overall adherence was
47% for gFOBT, 42% for FIT, 35% for FS, 28% for colo-
noscopy, and 22% for CTC.170 Only 62.4% of adults older
than 50 years in the United States report recent CRC
screening consistent with guideline recommendations, with
lower rates among American Indians and Alaska Natives
(48.4%), Hispanics (27.4%), and the uninsured (25.1%).171
As noted above, screening rates vary by age (only 45.3% of
adults aged 50-54 years report recent CRC screening vs
57.9% of adults aged 50-64 years and 71.8% for adults aged
65-75 years), by education (only 46.7% of adults with less
than a high school education report recent CRC screening
vs 70.7% of college graduates), and by insurance status (only
25.1% of uninsured adults report recent CRC screening vs
65.6% of insured adults).171
272 CA: A Cancer Journal for Clinicians
Optimizing adherence to CRC screening will require a
multipronged approach that addresses the barriers to screen-
ing at the individual, provider, organizational, and policy
levels with evidence-based interventions. Multicomponent
interventions to reduce structural barriers have been found
to have greater effects on utilization of colonoscopy and
FOBT than when single interventions were used.172
One of the most powerful factors for increasing adher-
ence to CRC screening is clinician recommendation. A sys-
tematic review reported overwhelming evidence that
provider recommendation significantly improves screening
rates.173 Furthermore, as noted above, it has been demon-
strated that offering patients a choice of CRC screening
tests rather than recommending a single test improves
adherence to screening and likely conveys to patients the
importance of the recommendation.
Several visit-based strategies have been shown to be effec-
tive in improving screening rates within practices and inte-
grated systems, especially reminder systems to help care
teams identify patients who are due for screening.46,174,175
Other effective visit-based strategies include “opportunistic
screening” or “in-reach” methods, including offering screen-
ing during nurse-driven influenza vaccination clinics.176-178
Evidence examining the impact of decision aids on CRC
screening adherence is mixed. Several systematic reviews
have found that, whereas decision aids increase screening
knowledge and modestly increase screening, there were no
significant differences in screening interest or behavior
among individuals who were exposed to decision aids com-
pared with those who were given general information about
CRC screening.46,79 A study examining the impact of com-
bining a decision aid with patient navigation in a diverse,
vulnerable patient population did demonstrate a strong
impact on screening completion but was unable to separate
the effects of the decision aid from patient navigation.179 A
recent study incorporating an iPad-based CRC decision aid
with test-ordering capability into the office visit demon-
strated a doubling of CRC screening completion from 15%
to 30% among vulnerable primary care patients who were
randomized to the intervention.180
Nonoffice-based strategies, including “outreach” strate-
gies whereby patients receive invitations to screening via
mail, have shown a 5% to 15% increase in adherence rates.
Mailed reminders with or without FIT kits/gFOBT cards
timed to a scheduled clinic appointment can increase screen-
ing.174,176,181-187 Open-access endoscopy has not been dem-
onstrated to increase scheduling of screening endoscopy,
although it is associated with higher procedure completion
rates.188
RCTs have shown that patient navigation is an effective
intervention for implementing stool-based and colonoscopy-
based screening programs. Navigation is particularly helpful

in increasing CRC screening in vulnerable popula-
tions.189-198 Investigators have offered helpful guidance on
key considerations when designing a successful navigation
program.199,200 Tailored patient navigation that allows the
patient’s care team to address specific patient barriers to
screening, including language, has been shown to be more
effective than standard navigation.195,196,201 Personal invita-
tion letters, preferably signed by the care provider, and
reminders mailed to all nonattendees are also highly effective
in enhancing CRC screening acceptance.202
Multifaceted interventions that target multiple levels of
care and consider factors outside the individual clinician’s
control represent the most effective strategies to enhance
CRC screening uptake and adherence, particularly in popu-
lations that have multiple barriers to CRC screening (eg,
financial barriers, lack of health insurance, low income, low
educational attainment, and language barriers). For exam-
ple, the ACA’s elimination of cost-sharing was associated
with an increase in utilization of CRC screening in adults
with low socioeconomic status likely because of the removal
of financial barriers.162 In community health center settings,
Baker et al found that, compared with usual care (computer-
ized reminders, standing orders for home FIT distribution
by medical assistants, and clinician feedback on CRC
screening rates), patients in an intervention group that also
received a mailed reminder letter, a free FIT with low-
literacy instructions, a postage-paid return envelope, and
automated follow-up telephone and text messages were
much more likely than those in usual care to complete
screening with a stool test (82.2% vs 37.3%; P < .001).203
After 2 years of follow-up, 71.6% of the intervention group
remained fully up to date with CRC screening.204 Several
organizations have compiled valuable resources to facilitate
the implementation of multifaceted interventions to increase
uptake of and adherence to CRC screening (see Supporting
Information).
Discussion
Changes From the Previous Guideline
The most notable change from the 2008 ACS guideline is
the recommendation for all average-risk adults to initiate
screening for CRC at age 45 years. In addition, the 2018
update provides more specific guidance regarding when to
discontinue CRC screening, which was not specifically
addressed in the previous guideline. The 2008 guideline
stated that CRC prevention should be the primary goal of
screening and that tests that detect both early cancer and
adenomatous polyps should be encouraged if resources are
available and the patient is willing to undergo an invasive
test. Although this update places value on both CRC inci-
dence and mortality reduction, the GDG chose not to pri-
oritize among screening tests, emphasizing instead that
CA CANCER J CLIN 2018;68:250–281
screening utilization and adherence could be improved and
the benefits of screening more fully achieved by offering a
choice of tests. This guideline includes 6 test options for
CRC screening: specifically, annual FIT or HSgFOBT, mt-
sDNA every 3 years, colonoscopy every 10 years, CTC every
5 years, and FS every 5 years. Recommended screening
intervals remain unchanged since 2008. Double-contrast
barium enema is no longer included as an acceptable screen-
ing option (see Supporting Information Table 1).
Considerations in Lowering the Starting Age to
45 Years
The overall quality of the evidence and the balance of bene-
fits and harms were judged to support a strong recommen-
dation for CRC screening in adults aged 50 years and older
with any of the included test options. Because until now the
recommended age to start has been 50 years, there is very
limited direct evidence to support a younger starting age
other than the 3 RCTs of gFOBT that started enrollment
at age 45 years, although no age-specific results have been
published.205-207 As soon as screening begins to occur regu-
larly in the group aged 45 to 49 years, observational evi-
dence on the performance and outcomes of screening will
accrue. The GDG relied on disease burden data and model-
ing studies to address the question of optimal starting age.
Thus, the starting age of 45 years has been designated as a
qualified recommendation given the limitations of the evi-
dence base.38 An absolute mortality benefit in younger age
groups will be lower than for older adults and, as some of
our reviewers have noted, there will be some increased
patient burden associated with a younger starting age. How-
ever, the recommendation places a high value on the poten-
tial years of life saved, addresses anticipated rising incidence
going forward, and is expected to contribute to the reduc-
tion in disparities in incidence before age 50 years in some
racial groups.33,34
In addition to the potential early detection and preven-
tion benefit for adults aged 45 to 49 years, lowering the
starting age to 45 years also is likely to have a favorable
impact on CRC incidence and incidence-based mortality in
the group ages 50 to 54 years. Incidence in this age group is
currently increasing, in contrast to the declining incidence
in all age groups after age 54 years.3
Implementation
The GDG acknowledged the implementation challenges
posed by lowering the starting age. First, changing the age
to begin screening—a key component of recommendations
that heretofore have achieved broad consensus—may con-
tribute to confusion and uncertainty among clinicians and
patients as to the best course of action. The ACS will seek
to mitigate the impact of conflicting recommendations
VOLUME 68 _ NUMBER 4 _ JULY/AUGUST 2018 273
 ACS Colorectal Cancer Screening Guideline
through clear communication of its recommendation and
rationale, including provider and patient support materials
(cancer.org/colonmd).86 Second, there will likely be a lag
between the publication of this recommendation and insur-
ance coverage by all providers of CRC screening starting at
age 45 years. The 2010 ACA requires that nongrandfathered
commercial insurance plans fully cover USPSTF-
recommended screening tests; these are minimum coverage
standards for an ACA-qualified health plan, and plans are
not restricted from extending CRC screening coverage to
individuals aged 45 to 49 years. Third, some have expressed
concerns that the US health care infrastructure will be unduly
strained by lowering the starting age to 45 years and that
efforts should focus instead on increasing screening rates in
adults aged 50 years and older. The ACS remains fully com-
mitted to increasing screening rates; both expanding the
screening to include adults aged 45 to 49 years and increasing
screening rates in the population aged 50 years and older can
be achieved within the current health care infrastructure. A
study that combined results from the 2012 Survey of Endo-
scopic Capacity with a modeling analysis indicated that
increasing screening rates to 80% (with any combination of
screening modalities) can be accommodated with current
excess capacity.76 In addition, this guideline places increased
emphasis on choice of screening options (not limited to colo-
noscopy) for those initiating CRC screening.
Patient Choice and Decision Making
Whereas past CRC screening guidelines have prioritized
specific tests or specific outcomes (ie, prevention), in this
update, the GDG chose to prioritize the opportunity for
patients to select either a structural (visual) examination or a
high-sensitivity stool-based test, depending on their prefer-
ence and test availability. This decision does not discount
the argument that clinicians and the target population also
desire expert advice. However, too many adults who are
advised to undergo CRC screening with colonoscopy do not
adhere to the advice from the referring provider, and the
opportunity to be adherent with CRC screening is missed
because of multiple factors, including the failure to ascertain
the patient’s willingness to undergo an invasive procedure.
Health professionals should be prepared to describe and
offer options for a structural examination and a stool test
and to discuss additional options if the patient does not
appear to be accepting of the tests initially presented. As
detailed in Table 3, the screening options differ in several
ways that influence patient choice. The information pro-
vided is designed to facilitate clinician-patient encounters
and patient choices consistent with their preferences and
thus increase utilization of CRC screening. In addition,
materials to facilitate test selection at the point of care have
been developed by the ACS.86,87
274 CA: A Cancer Journal for Clinicians
Comparison With Other Guidelines
The USPSTF updated their CRC screening guideline in
2016.44 CRC screening from ages 50 through 75 years with
any of 7 screening strategies was given an “A” recommenda-
tion (comparable to a strong recommendation using
GRADE criteria), which largely overlaps with the 2018
ACS recommendations. The primary differences are as fol-
lows: ACS recommends beginning screening at age 45
years, while the USPSTF recommends beginning at age 50
years and the USPSTF recommends FS every 10 years com-
bined with annual FIT, which is not included in the ACS
list of testing options. The ACS GDG relied upon RCT
evidence supporting a 5-year screening interval for FS alone,
as well as the results of modeling commissioned for this
guideline, and concluded that the FS-only option at a
5-year interval should be maintained. The modeling data
suggested that any incremental benefit conferred by the
combined strategy would be small compared with model-
recommended strategies for either test alone, and there also
would be the complexity of integrating 2 test schedules.
Finally, the GDG expressed concerns about even continuing
to endorse FS, given the low availability and utilization in
the United States (see Supporting Information Table 1).
In 2017 the USMSTF preferentially recommended
screening with colonoscopy every 10 years, annual FIT for
individuals declining colonoscopy, and, as second-tier tests,
CTC every 5 years, mt-sDNA every 3 years, and FS every 5
to 10 years.57 The USMSTF recommended that African
Americans initiate screening at age 45 years and that
average-risk adults belonging to other racial/ethnic groups
begin screening at age 50 years. For individuals with no ade-
nomatous findings or CRC at prior screening, the
USMSTF recommended discontinuing screening at age 75
years or when life expectancy is less than 10 years; and they
recommended continuing screening to age 85 years for
those not previously screened, depending on comorbidities
(see Supporting Information Table 1).
Screening in Individuals at Increased or High Risk
for CRC
This guideline update focuses on CRC screening in
average-risk adults and does not address screening or sur-
veillance in persons at increased or high risk for developing
CRC. These include individuals with history of adenoma-
tous polyps, a personal history of CRC, a family history of
CRC or adenomatous polyps diagnosed in a relative before
age 60 years, a personal history of inflammatory bowel dis-
ease, a confirmed or suspected hereditary CRC syndrome,
or a history of abdominal or pelvic radiation for a previous
cancer.18-21 Updated screening and surveillance recommen-
dations for these groups have been developed by other
organizations.208-211 Identification of candidates for

differential screening requires adequate collection and
updating of family history information and appropriate
referral for genetic counseling and testing of individuals at
increased risk for hereditary syndromes.
Limitations
The recommendation to initiate screening at age 45 years
is based on limited empirical data related to outcomes in
average-risk individuals who initiate screening between
ages 45 and 49 years. The decision to begin screening in
average-risk adults at aged 50 years, in both clinical prac-
tice and research, has been largely based on expert opinion
about an appropriate threshold for the burden of disease,
and this practice understandably has limited the available
evidence on screening outcomes in adults aged 45 to 49
years. However, the increasing CRC incidence in succes-
sive birth cohorts and subsequent, recent increases in mor-
tality in the group ages 50 to 54 years suggest an
opportunity to address a well recognized trend and miti-
gate future increased incidence and mortality. In the pres-
ence of the changing epidemiology of CRC, it is
important to acknowledge that the desired empirical evi-
dence (ie, prospective data on screening outcomes in
adults aged 45-49 years), conservatively, would be a
decade or more away even if a large study were launched
this year. In the 5 years before the conventionally accepted
age to begin screening, there is little evidence to suggest
that screening would be less effective in detecting occult
blood or advanced neoplasia, apart from the lower but
increasing prevalence of disease.
The modeling analysis that supported the recommenda-
tion for an earlier starting age did not examine the use of
alternating modalities or of combination or hybrid screening
strategies. Hybrid strategies have been proposed as a means
of decreasing the burden of screening from either an indi-
vidual or a societal perspective.96 For example, switching
from colonoscopy to a stool-based test or CTC at older ages
could theoretically reduce exposure to the higher complica-
tion risk associated with colonoscopy with advancing age.
With greater confidence about the influence of prior find-
ings on future risk, CRC screening test choice, interval, and
stopping age might be tailored based on prior results. This
is an area in need of further research, both to determine
which hybrid strategies would be most effective and accept-
able to the target population and to address the challenge of
implementing different hybrid strategies in the primary care
setting.
Conclusions
Since the last update of the ACS CRC screening guideline
a decade ago, there have been numerous developments in
the field of CRC screening that have informed this update.
CA CANCER J CLIN 2018;68:250–281
Although the 6 screening options presented in this guide-
line have not fundamentally changed, the accrual of experi-
mental, observational, and modeling data has served to
validate their role in CRC screening and further reinforce
the conclusion that the benefits of regular screening with
any of the tests in terms of CRC mortality and incidence
reduction significantly outweigh the risks and burdens they
confer.
One of the most significant and disturbing developments
in CRC is the marked increase in CRC incidence—particu-
larly rectal cancer—among younger individuals. While the
causes of this increase are not understood, it has been
observed in all adult age groups below the age when screen-
ing has historically been offered and is contributing signifi-
cantly to the burden of suffering imposed by premature
CRC mortality. Incorporating this epidemiological shift
into contemporary modeling of CRC screening demon-
strated that the benefit-burden balance is improved by low-
ering the age to initiate CRC screening to 45 years.
Lowering the starting age is expected to benefit not only the
segments of the population who suffer disproportionately
from CRC—blacks, Alaska Natives, and American
Indians—but also those individuals otherwise considered to
be at average risk. Moreover, epidemiological trends in
cohorts as young as those born in 1990 suggest that the
higher risk of developing CRC will be a persistent concern
for decades to come.
As outlined in this guideline, there have been substantive
advances in our understanding of strategies to overcome
barriers to CRC screening through interventions at the
patient, provider, office, and system levels that serve to
increase uptake of and adherence to screening. Yet, with
almost 40% of eligible adults not up to date with CRC
screening, it is clear that these interventions too often are
not being implemented. Reaching the full potential of CRC
screening in the United States will require multifaceted
approaches tailored to the individual patient and practice
setting. These approaches vary in intensity and resource uti-
lization, but even an intervention as simple as offering a
choice of screening test to improve uptake—as emphasized
in this guideline—is expected to further the goal of improv-
ing screening rates and reducing the burden of suffering
from CRC.
In conclusion, the ACS recommends that all US adults
at average risk of CRC undergo regular screening with
any of the 6 options outlined in this guideline, beginning
at age 45 years. Adults in good health should continue
screening until age 75 years, beyond which the decision to
continue screening should be individualized based on
patient preferences, health status, life expectancy, and
screening history. Ascribing to the adage that the best
CRC screening test is the one that gets done, and done
VOLUME 68 _ NUMBER 4 _ JULY/AUGUST 2018 275
 ACS Colorectal Cancer Screening Guideline

well, the ACS recommends that patients initiating screen-
ing or previously nonadherent with screening be offered a
choice of tests based on availability of high-quality
options. It is our hope that widespread adoption of this
guideline will have a major impact on the incidence, suf-
fering, and mortality caused by CRC. 䊏
Acknowledgments: We thank Amy Allison, MPH, MLS, and Shenita Peter-
son, MPH (Woodruff Health Sciences Center Library, Emory University), for
assistance with literature searches to update and supplement the evidence
review. We also thank Michael Bonow (Intern, Emory University Rollins
School of Public Health) for assistance with supplemental literature review and
evidence synthesis. In addition, we thank the expert advisory panel (listed in
the online Supporting Information) for their time and expertise throughout the
guideline update and the representatives of stakeholder organizations (listed in
the Supporting Information) who reviewed the draft recommendations and
rationale. Finally, we thank our colleagues from the Cancer Intervention and
Surveillance Modeling Network for their analyses and review of the article
(Amy Knudsen, PhD; Iris Lansdorp-Vogelaar, PhD; Reinier Meester, PhD;
Elisabeth Peterse, MSc; and Ann Zauber, PhD).

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